Multi-cyclic IRAK1 and IRAK4 inhibiting compounds and uses thereof

Abstract

The present disclosure provides a method of treating an inflammatory disease or disorder, acute myeloid leukemia (AML), or myelodysplastic syndrome (MDS) in a subject, the method comprising administering to the subject a compound that inhibits IRAK1 and IRAK4. The present disclosure further provides a method of determining a subject with a disease / disorder that can be treated by the administration of a compound which inhibits IRAK1 and IRAK4.

Description

[0001]TITLE Multi-Cyclic IRAK1 and IRAK4 Inhibiting Compounds and Uses Thereof CROSS-REFERENCE TO RELATED APPLICATIONS The present application is an international application claiming priority to U.S. Provisional Application No.63 / 516,771, filed July 31, 2023, U.S. Provisional Application No. 63 / 578,386, filed August 24, 2023, and U.S. Provisional Application No.63 / 598,011, filed November 10, 2023, each of which is incorporated by reference herein in its entirety. GOVERNMENT RIGHTS This invention was made in the performance of a Cooperative Research and Development Agreement with the National Institutes of Health, an Agency of the Department of Health and Human Services. The Government of the United States has certain rights in this invention. SEQUENCE LISTING The instant application contains a Sequence Listing which has been submitted electronically in.XML format and is hereby incorporated by reference in its entirety. The .XML copy, created on July 29, 2024, is named “130364-5012.xml” and is 18 KB in size. BACKGROUND IRAKs are a family of related kinases that operate at the nexus of multiple innate immune and inflammatory pathways implicated in myeloid malignancies. There is increasing interest in the role of the IRAK kinases as targets in the treatment of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) (reviewed in J Bennett and DT Starczynowski, Curr Opin Hematol 2022). IRAK1 and IRAK4 lie downstream of multiple receptors that stimulate the canonical NF-kB signaling pathway upstream of TRAF6 via the myddosome complex. While TRAF6 is necessary to preserve the tonic NF-kB signaling that is required for hematopoietic stem cell (HSC) homeostasis (J Fang et. al. Cell Reports 2018), overactivity of the NF-kB signaling pathway has been implicated in both MDS and AML (reviewed in MCJ Bosman et. al., Crit Rev Oncol / Hematol 2016; JJ Trowbridge and DT Starczynowski, J Exp Med 2021). The requirement for both IRAK1 and IRAK4 in this pathway has been explored using both genetic DB1 / 147901903.2 1 and pharmacologic technologies. The use of genetic loss-of-function approaches revealed that deletion and / or inhibition of IRAK4 results in a compensatory increase in IRAK1 protein and activation (data unpublished), suggesting that high potency antagonism of both kinases will be required for optimal inhibition of NF-kB-mediated transcriptional responses in disease- propagating MDS and AML cells. IRAK4 inhibitors have advanced into clinical trials for MDS and AML validating IRAK4 as a therapeutic target. Early data from these trials has been encouraging; however, the overall responses remain modest. MDS and AML exist along a continuous disease spectrum starting with early-stage MDS, which may progress to high-risk (HR) MDS and / or AML. AML is a heterogeneous malignancy characterized by suppression of normal hematopoiesis and overproduction of immature myeloid blast cells associated with a differentiation block. Most patients with HR-MDS and AML are not cured with available therapies, underscoring the urgent need for new therapeutic alternatives that will improve the clinical outcomes of these patients. Despite significant effort, the five-year relative survival of AML patients remains at only 25%. MDS and AML originate in hematopoietic stem and progenitor cells (HSPC, referred to as leukemic stem / progenitor cells [LSPC]) that acquire genetic and / or epigenetic abnormalities. A pool of LSPCs persist throughout the course of disease to replenish the bulk leukemic blast cells and contribute to treatment-related relapse when not eradicated. Recent therapies, such as Venetoclax with Azacytidine and Menin inhibitors, that target the LSPCs have shown improved clinical outcomes for patients with HR-MDS and AML. LSPCs also share cellular states and transcriptional programs with normal HSPCs, such as ones that maintain multi-potent self-renewal properties and prevent untimely differentiation. Like normal HSPCs, LSPCs have acquired an undifferentiated state that permits long-term expansion of progeny cells, properties which have been evaluated using surrogate in vitro progenitor assays (i.e., colony assays in methylcellulose) and in vivo hematopoietic transplantation models. Uncovering targetable signaling dependencies unique to LSPCs is critical to improve therapeutic responses in patients. It was recently reported that patient-derived LSPCs from HR- MDS and across various AML subtypes exhibit a high frequency of dysregulated immune and inflammatory pathways. Dysregulation of immune-related genes is observed in >50% of MDS and AML, and chronic innate immune pathway activation increases the risk of developing myeloid malignancies. Moreover, a significant number of genetic and molecular alterations in DB1 / 147901903.2 2 MDS and AML directly impinge on effectors of the Toll-like receptor (TLR) and Interleukin 1 receptor (IL-1R) pathways, both of which converge on a signaling complex operated by the interleukin-1 receptor associated kinases (IRAK): IRAK1, IRAK2, and IRAK4. In the context of normal immune cell biology, activation of TLRs or IL-1R leads to recruitment of the adaptor protein MyD88, which then nucleates an oligomeric signaling complex (Myddosome) that includes MyD88 and IRAK4. IRAK4 subsequently recruits and phosphorylates IRAK1 or IRAK2, which then induces multiple downstream effectors, including NF-kB and MAPKs. Chronic activation of this MyD88-IRAK canonical signaling axis is presumed to underly malignant hematopoiesis in MDS / AML, a theory that is partially supported by the discovery of activating mutations in MyD88 that cause spontaneous assembly of the Myddosome complex in lymphomas. Consequently, IRAK4 inhibitors and proteolysis targeting chimeric (PROTAC) small molecule degraders are undergoing evaluation in pre-clinical studies and early phase clinical trials for hematologic malignancies and inflammatory conditions. The IRAK4 kinase inhibitor PF-06650833 (Zimlovisertib) is being evaluated for chronic inflammatory disorders, while CA-4948 (Emavusertib) is being evaluated in hematologic malignancies, including lymphoma, HR- and low-risk (LR)-MDS, and refractory / relapsed AML. The IRAK4 PROTACs, KT-474 and KT-413, are being evaluated in immuno-inflammatory disease and MyD88-mutant lymphomas, respectively. Safety data from these trials have revealed minimal on-target toxicity nor adverse effects, suggesting that targeting IRAK4 will have an acceptable safety profile and tolerability. Initial results from the early phase trials in HR-MDS and AML with CA-4948 showed complete or partial response rates of ~40% and additional patients having reductions in leukemic blast counts. Interestingly, 40% of AML patients with spliceosome mutations reached a complete response (CR) or CR with partial hematologic recovery (CRh), while 57% of HR-MDS patients achieved a CR. These clinical observations support the recent findings that mutations in the splicing factors U2AF1 and SF3B1 directly induce hypermorphic IRAK4 isoforms and active innate immune signaling in MDS and AML. The data emerging from the ongoing clinical studies suggest that IRAK4 is a relevant target in hematologic malignancies. However, the magnitude of clinical responses appears to depend on genetic background and suggests inadequacy of IRAK4 inhibitors as monotherapy. Thus, a better understanding of IRAK4 signaling is necessary to refine therapeutic strategies targeting dysregulated innate immune and inflammatory signaling in hematologic malignancies. DB1 / 147901903.2 3 The present disclosure addresses this unmet need. SUMMARY OF THE DISCLOSURE In one aspect, the present disclosure provides a method of treating an inflammatory disease or disorder, or a cancer selected from acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), in a subject in need thereof, the method comprising administering to the subject Compound 8: or a salt, ester, solvate, optical of an isomer thereof. In one embodiment, the inflammatory disease or disorder is selected from chronic inflammation, sepsis, rheumatoid arthritis, hidradenitis suppurativa, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, psoriasis, Sjögren’s syndrome, Ankylosing spondylitis, systemic sclerosis, Type 1 diabetes mellitus, Crohn’s disease, atopic dermatitis, and colitis. In one embodiment, the AML is relapsed AML, refractory AML, relapsed / refractory AML, AML with resistance to hypomethylating agents, AML with resistance to venetoclax, AML with resistance to hypomethylating agents and venetoclax, monocytic AML, or monocytic-like AML, or the MDS is MDS with a mutation in isocitrate dehydrogenase 1, MDS with a mutation in isocitrate dehydrogenase 2, or MDS with a splicing factor mutation, optionally wherein the MDS with a splicing factor mutation comprises MDS with a splicing factor mutation in U2AF1, SRSF2, SF3B1, or ZRSR2. In one embodiment, the subject has AML and the subject has a gene mutation in one or more of FLT3, TET2, KIT, BCOR, BRAF, CDKN2A, UTX, ZRSR2, NPM1, PTEN, DNMT3A, EZH2, RUNX1, JAK2, ASXL1, ABL1, ATRX, BCORL1, KDM6A, PTPN11, TP53, CBL, CEBPA, FBXW7, HRAS, NRAS, IDH1, IDH2, NRAS, PDGFRA, SF3B1, ETV6, PHF6, GNAS, KRAS, NOTCH1, STAG2, SETBP1, GATA1, GATA2, WT1, SRSF2, GNAS, CEBPA, CALR, MPL, BCL11A, ATM, CTCF, U2AF1, TYK2, FBX, RUI, RAD21, or MLL3, or the subject has MDS and the subject has a gene mutation in one or more of DB1 / 147901903.2 4 U2AF1, FLT3, ASXL1, BCORL1, BRAF, CBL, CDKN2A, DNMT3A, FBXW7, GATA2, IDH2, KRAS, NOTCH1, NRAS, PDGFRA, PTEN, PTPN11, TET2, TP53, EZH2, HRAS, KIT, MPL, PHF6, RUNX1, WT1, ABL1, CEBPA, ETV6, IDH2, KDM6A, KIT, KRAS, PTEN, RUNX1, SF3B1, or ZRSR2. In one embodiment, Compound 8 has an IRAK1 IC50 of less than about 40 nM, optionally less than about 5 nM, and / or a FLT3 IC50 of less than about 2.5 nM. In one embodiment, Compound 8 has an IRAK4:IRAK1 inhibitory potency ratio of less than about 40. In one embodiment, the subject in need thereof has elevated expression of one or more IRAK1 / 4-associated genes and / or decreased expression of one or more IRAK1 / 4-associated genes. In one embodiment, the subject in need thereof has elevated expression and / or decreased expression of one or more IRAK1 / 4-associated genes compared to a healthy control subject. In one embodiment, the subject in need thereof has elevated expression of one or more IRAK1 / 4- associated genes selected from: PLS3, HSBP1L1, CDC42BPA, PPP2R3A, GNG12, PENK, STC2, DNAJC22, SH3D19, GABRD, RAVER2, ARHGEF26, APBB2, BAI2, DPEP1, LGI2, PIP5K1A, SOX18, BMP4, TMC4, KCNIP3, CCNO, ULK4P2, FAM57A, SCARA3, CERS1, BEND5, HAPLN3, DNMBP, KIAA1522, PIR, GTF3C5 ECHDC3, ICAM1, RAB3A, SDHA, C9orf116, MKI67, LMTK3, MCM10, ADM2, HSD17B14, LOC102724002, KCNH2, PRAME, KIAA1279, LOC101929974, ARHGAP21, SULT2B1, ADCY6, GBF1, TUBGCP2, CD19, SPIRE2, SH3PXD2B, AADAT, FOXC1, ZBED3, TSKU, NRARP, AMIGO2, PCBD1, TCAM1P, FAM57B, LOC101929021, PCK2, CCDC127, MGMT, C6orf147, TGFB1I1, DPP4, ALX4, TACC2, WLS, PACSIN3, NAPA-AS1, LINC00999, BAIAP3, ANKH, VDAC2, TAF3, ECHS1, EFNA3, CORO6, TCTN2, HPS1, DNAJB12, SPIB, SLC29A3, PHGDH, PTMS, TMEM91, SEC24C, HGD, MSS51, TEAD3, LARP4B, ZCCHC24, ARHGEF16, FOXO6, FBXO18, PPRC1, CCDC78, RHBDL1, SPINT1, STON2, NUDT8, NEBL, EPAS1, FAM178A, PI4K2A, SNED1, STAM, PLOD2, TM7SF2, FGD1, PCDHB6, CCNB3, MCMDC2, EDRF1, NRM, PPIF, ATF5, BRD9, B3GALT4, NET1, TMEM169, RPH3AL, DROSHA, RBMS2, POLR3A, TRIP13, LPHN1, ZMIZ1, RP11-344B5.2, HNRNPF, HSD17B7P2, SLIT1, LOC648987, ACTR1A, CCT5, S1PR5, WDFY4, GRK5, SREBF1, STXBP5L, VARS2, GAB2, ZFP36L1, CPNE7, HSPA2, NAT8L, DOK4, IGF1R, KHK, KIRREL2, COMTD1, ZNF488, CASC10, QRICH2, RBM17, LSS, PAX8, PKN3, HELLS, FN3K, CDC42EP1, NFIX, BMS1, STOX1, SEMA4B, SUPV3L1, FAM198A, RCOR2, PDCD, PPAP2A, DDX12P, ACY3, TSPAN10, NUP155, RIBC2, PLCXD1, TP53INP2, GOLPH3, WDR70, BTRC, SVIL, DTX4, DB1 / 147901903.2 5 DUSP5, ECE1, MRPL43, SKP2, SNHG3, MYRF, ZFYVE27, H2AFY2, NOLC1, SLC25A28, WNK2, NDUFS6, SLC30A3, LOC642846, NEURL1B, ARMC4, SFXN3, VASH2, NOTUM, VCL, LOC100506901, CSTF2T, PRICKLE1, ZNF132, GPR153, ZMYND11, DGCR5, OXER1, VTI1A, PCDHGC3, MORC4, EIF3A, PDCD11, SLC38A1, MC1R, CBS, AC002454.1, PDCD6, B4GALNT1, RPP38, SUGT1P1, NEDD4L, PROCA1, SH3PXD2A, JAG2, FGFR3, TMEM191B, SEPHS1, LOC100505761, C21orf58, FADS1, TET1, GBGT1, KAT6B, KIFC2, TAF5, CASP7, PELI3, PP7080, ATN1, KIAA1598, FAM115A, NKX3-2, CHCHD10, GPSM1, LRP4, CDT1, EIF4EBP2, AASS, ABCC6P1, ABCD2, ADAMTS14, AGAP4, AGAP9, AIFM2, AKR1C1, AKR1E2, ANK3, ANKRD33B, ANO6, APBB1IP, ARHGAP19, ARNTL2, ARSG, ARTN, ASCC1, ASUN, BAG3, BEND4, BEX5, BLNK, BTAF1, C10orf10, C10orf12, C10orf76, C10orf91, C15orf38, C2CD4C, C2CD5, C3orf18, CALHM2, CAMK1D, CAPRIN2, CDH2, CDHR1, CEL, CEP72, CES3, CES4A, CHST3, CLIC5, CMAS, CNNM2, CNTN1, COL27A1, COL4A5, CPS1, CRABP1, CTBP2, CUEDC2, CXorf57, DAPK2, DDAH2, DDX11, DDX11-AS1, DENND5B, DHTKD1, DNM1L, DPCD, DPY19L2, DUSP5P1, EBF3, EFEMP2, EGFR, ELK1, EPHB4, FAM155B, FAM175B, FAM21C, FAM45A, FAM53B, FAM84B, FCER2, FGD4, FOXL2, FZD8, GAS1, GPC6, GRIA3, GUCY1B3, GYPE, HDHD3, HES4, HIF1AN, HMGCS1, HMX2, HMX3, HOXB13, HOXB6, HSD17B8, HSH2D, IDE, INPP5A, INPP5F, INPP5J, IPO8, IRAK4, ITPR2, ITPR3, JMJD1C, KAZALD1, KCNQ5, KCNS3, KIAA1324, KIF11, KLHL42, KLLN, KRAS, KREMEN2, LAT, LDB1, LGALS3BP, LINC00477, LIPE, LOC100288152, LOC100506688, LOC100506691, LOC100507487, LOC101927104, LOC101927799, LOC101928913, LOC102723337, LOC102724472, LPCAT1, LRMP, LRRC10B, LRRC20, LRRC27, LTK, LY6G5C, LZTS2, MAP2K6, MASTL, MCIDAS, MCMBP, MDGA2, METTL12, METTL20, MMS19, MPPED2, MRPS16, MRPS35, MSX1, MX1, NDUFB8, NEURL1, NEUROG3, NFKB2, NIM1K, NKD2, NLGN2, NNT, NNT-AS1, NT5DC2, NUDT13, OGDHL, OVOL2, OXCT1, P2RX7, P4HA1, PABPC1L, PANK1, PAOX, PAPD7, PAPSS2, PCDHB13, PCDHB14, PCED1B, PCED1B-AS1, PCSK5, PDLIM1, PEAR1, PFKP, PGAM1, PGAM4, PI15, PITX1, PLEKHA8P1, PLEKHO1, PPFIBP1, PPP2R2D, PPP3CB, PRTFDC1, PSTPIP2, PTENP1, PVRL3, PWWP2B, PXDC1, RNF208, ROBO1, RP11-184I16.4, RP11-53O19.1, RP11-96H19.1, RPAP3, RTN1, SAMD11, SAMD8, SCAF11, SCD5, SDHAP3, SEC14L2, SEC31B, SEC61A2, SECTM1, SFMBT2, SFXN2, SHANK3, SHISA3, SHISA7, SIDT1, SKIDA1, SLA2, SLC12A7, SLC16A6, SLC16A9, SLC4A11, DB1 / 147901903.2 6 SLITRK5, SMAD1, SNHG12, SNORA61, SNORD104, SOX1, SPEF2, SRRM3, SUFU, TARS, TCF7, TEX15, TGFBR3L, THBD, TIAL1, TLX3, TM7SF3, TMEM180, TMEM191C, TMEM255A, TMEM63C, TRIM72, TUBB3, TYSND1, UGT3A2, ULK2, UNC13D, USP54, VENTX, VIM, XPNPEP1, YARS2, YPEL3, ZDHHC16, ZDHHC6, ZNF43, ZNF438, ZNF503, ZNF503-AS2, ZNF511, ZNF574, ZNF622, ZNF726, ZNF99, ZWINT, ADM, ALDOC, BNIP3, CA3, CD209, CSMD3, DDIT4, FCGR2B, FCGR2C, FIGN, GLIS2, SHISA8, SOX5, TBC1D30, TLE6, TLX1, VAT1L, VEGFA, ANXA4, APLN, C1QL4, CCDC102A, CHDH, EGLN3, ENO2, FADS2, HK2, HSPA7, IL17RB, KLF2, LAMC, LINC00263, LOC101928092, LOC102724908, MIR210HG, NRTN, PFKFB4, SCD, SLC4A3, SLC6A8, ZNF215, and ZNF395, optionally the subject in need thereof has elevated expression of one or more IRAK1 / 4- associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3. In one embodiment, the subject in need thereof has decreased expression of one or more IRAK1 / 4-associated genes selected from: PLS3, HSBP1L1, CDC42BPA, PPP2R3A, GNG12, PENK, STC2, DNAJC22, SH3D19, GABRD, RAVER2, ARHGEF26, APBB2, BAI2, DPEP1, LGI2, PIP5K1A, SOX18, BMP4, TMC4, KCNIP3, CCNO, ULK4P2, FAM57A, SCARA3, CERS1, BEND5, HAPLN3, DNMBP, KIAA1522, PIR, GTF3C5 ECHDC3, ICAM1, RAB3A, SDHA, C9orf116, MKI67, LMTK3, MCM10, ADM2, HSD17B14, LOC102724002, KCNH2, PRAME, KIAA1279, LOC101929974, ARHGAP21, SULT2B1, ADCY6, GBF1, TUBGCP2, CD19, SPIRE2, SH3PXD2B, AADAT, FOXC1, ZBED3, TSKU, NRARP, AMIGO2, PCBD1, TCAM1P, FAM57B, LOC101929021, PCK2, CCDC127, MGMT, C6orf147, TGFB1I1, DPP4, ALX4, TACC2, WLS, PACSIN3, NAPA-AS1, LINC00999, BAIAP3, ANKH, VDAC2, TAF3, ECHS1, EFNA3, CORO6, TCTN2, HPS1, DNAJB12, SPIB, SLC29A3, PHGDH, PTMS, TMEM91, SEC24C, HGD, MSS51, TEAD3, LARP4B, ZCCHC24, ARHGEF16, FOXO6, FBXO18, PPRC1, CCDC78, RHBDL1, SPINT1, STON2, NUDT8, NEBL, EPAS1, FAM178A, PI4K2A, SNED1, STAM, PLOD2, TM7SF2, FGD1, PCDHB6, CCNB3, MCMDC2, EDRF1, NRM, PPIF, ATF5, BRD9, B3GALT4, NET1, TMEM169, RPH3AL, DROSHA, RBMS2, POLR3A, DB1 / 147901903.2 7 TRIP13, LPHN1, ZMIZ1, RP11-344B5.2, HNRNPF, HSD17B7P2, SLIT1, LOC648987, ACTR1A, CCT5, S1PR5, WDFY4, GRK5, SREBF1, STXBP5L, VARS2, GAB2, ZFP36L1, CPNE7, HSPA2, NAT8L, DOK4, IGF1R, KHK, KIRREL2, COMTD1, ZNF488, CASC10, QRICH2, RBM17, LSS, PAX8, PKN3, HELLS, FN3K, CDC42EP1, NFIX, BMS1, STOX1, SEMA4B, SUPV3L1, FAM198A, RCOR2, PDCD4, PPAP2A, DDX12P, ACY3, TSPAN10, NUP155, RIBC2, PLCXD1, TP53INP2, GOLPH3, WDR70, BTRC, SVIL, DTX4, DUSP5, ECE1, MRPL43, SKP2, SNHG3, MYRF, ZFYVE27, H2AFY2, NOLC1, SLC25A28, WNK2, NDUFS6, SLC30A3, LOC642846, NEURL1B, ARMC4, SFXN3, VASH2, NOTUM, VCL, LOC100506901, CSTF2T, PRICKLE1, ZNF132, GPR153, ZMYND11, DGCR5, OXER1, VTI1A, PCDHGC3, MORC4, EIF3A, PDCD11, SLC38A1, MC1R, CBS, AC002454.1, PDCD6, B4GALNT1, RPP38, SUGT1P1, NEDD4L, PROCA1, SH3PXD2A, JAG2, FGFR3, TMEM191B, SEPHS1, LOC100505761, C21orf58, FADS1, TET1, GBGT1, KAT6B, KIFC2, TAF5, CASP7, PELI3, PP7080, ATN1, KIAA1598, FAM115A, NKX3-2, CHCHD10, GPSM1, LRP4, CDT1, EIF4EBP2, AASS, ABCC6P1, ABCD2, ADAMTS14, AGAP4, AGAP9, AIFM2, AKR1C1, AKR1E2, ANK3, ANKRD33B, ANO6, APBB1IP, ARHGAP19, ARNTL2, ARSG, ARTN, ASCC1, ASUN, BAG3, BEND4, BEX5, BLNK, BTAF1, C10orf10, C10orf12, C10orf76, C10orf91, C15orf38, C2CD4C, C2CD5, C3orf18, CALHM2, CAMK1D, CAPRIN2, CDH2, CDHR1, CEL, CEP72, CES3, CES4A, CHST3, CLIC5, CMAS, CNNM2, CNTN1, COL27A1, COL4A5, CPS1, CRABP1, CTBP2, CUEDC2, CXorf57, DAPK2, DDAH2, DDX11, DDX11-AS1, DENND5B, DHTKD1, DNM1L, DPCD, DPY19L2, DUSP5P1, EBF3, EFEMP2, EGFR, ELK1, EPHB4, FAM155B, FAM175B, FAM21C, FAM45A, FAM53B, FAM84B, FCER2, FGD4, FOXL2, FZD8, GAS1, GPC6, GRIA3, GUCY1B3, GYPE, HDHD3, HES4, HIF1AN, HMGCS1, HMX2, HMX3, HOXB13, HOXB6, HSD17B8, HSH2D, IDE, INPP5A, INPP5F, INPP5J, IPO8, IRAK4, ITPR2, ITPR3, JMJD1C, KAZALD1, KCNQ5, KCNS3, KIAA1324, KIF11, KLHL42, KLLN, KRAS, KREMEN2, LAT, LDB1, LGALS3BP, LINC00477, LIPE, LOC100288152, LOC100506688, LOC100506691, LOC100507487, LOC101927104, LOC101927799, LOC101928913, LOC102723337, LOC102724472, LPCAT1, LRMP, LRRC10B, LRRC20, LRRC27, LTK, LY6G5C, LZTS2, MAP2K6, MASTL, MCIDAS, MCMBP, MDGA2, METTL12, METTL20, MMS19, MPPED2, MRPS16, MRPS35, MSX1, MX1, NDUFB8, NEURL1, NEUROG3, NFKB2, NIM1K, NKD2, NLGN2, NNT, NNT-AS1, NT5DC2, NUDT13, OGDHL, OVOL2, OXCT1, P2RX7, P4HA1, PABPC1L, PANK1, PAOX, DB1 / 147901903.2 8 PAPD7, PAPSS2, PCDHB13, PCDHB14, PCED1B, PCED1B-AS1, PCSK5, PDLIM1, PEAR1, PFKP, PGAM1, PGAM4, PI15, PITX1, PLEKHA8P1, PLEKHO1, PPFIBP1, PPP2R2D, PPP3CB, PRTFDC1, PSTPIP2, PTENP1, PVRL3, PWWP2B, PXDC1, RNF208, ROBO1, RP11-184I16.4, RP11-53O19.1, RP11-96H19.1, RPAP3, RTN1, SAMD11, SAMD8, SCAF11, SCD5, SDHAP3, SEC14L2, SEC31B, SEC61A2, SECTM1, SFMBT2, SFXN2, SHANK3, SHISA3, SHISA7, SIDT1, SKIDA1, SLA2, SLC12A7, SLC16A6, SLC16A9, SLC4A11, SLITRK5, SMAD1, SNHG12, SNORA61, SNORD104, SOX1, SPEF2, SRRM3, SUFU, TARS, TCF7, TEX15, TGFBR3L, THBD, TIAL1, TLX3, TM7SF3, TMEM180, TMEM191C, TMEM255A, TMEM63C, TRIM72, TUBB3, TYSND1, UGT3A2, ULK2, UNC13D, USP54, VENTX, VIM, XPNPEP1, YARS2, YPEL3, ZDHHC16, ZDHHC6, ZNF43, ZNF438, ZNF503, ZNF503-AS2, ZNF511, ZNF574, ZNF622, ZNF726, ZNF99, ZWINT, ADM, ALDOC, BNIP3, CA3, CD209, CSMD3, DDIT4, FCGR2B, FCGR2C, FIGN, GLIS2, SHISA8, SOX5, TBC1D30, TLE6, TLX1, VAT1L, VEGFA, ANXA4, APLN, C1QL4, CCDC102A, CHDH, EGLN3, ENO2, FADS2, HK2, HSPA7, IL17RB, KLF2, LAMC, LINC00263, LOC101928092, LOC102724908, MIR210HG, NRTN, PFKFB4, SCD, SLC4A3, SLC6A8, ZNF215, and ZNF395, optionally the subject in need thereof has decreased expression of one or more IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3. In one embodiment, upon administration to the subject, Compound 8 decreases the expression of one or more IRAK1 / 4-associated genes found to be elevated in the subject, and / or increases the expression of one or more IRAK1 / 4-associated genes found to be decreased in the subject. In one embodiment, the administration of Compound 8 decreases the expression of the one or more IRAK1 / 4-associated genes found to be elevated in the subject before the administration of Compound 8, and / or increases the expression of the one or more IRAK1 / 4-associated genes found to be decreased in the subject before the administration of Compound 8. In one embodiment, the administration of Compound 8 decreases the expression of one or more IRAK1 / 4-associated genes found to be elevated in the subject compared to a healthy control DB1 / 147901903.2 9 subject, and / or increases the expression of one or more IRAK1 / 4-associated genes found to be decreased in the subject compared to a healthy control subject. In one embodiment, upon administration to the subject, Compound 8 decreases the expression of one or more IRAK1 / 4- associated genes selected from: PLS3, HSBP1L1, CDC42BPA, PPP2R3A, GNG12, PENK, STC2, DNAJC22, SH3D19, GABRD, RAVER2, ARHGEF26, APBB2, BAI2, DPEP1, LGI2, PIP5K1A, SOX18, BMP4, TMC4, KCNIP3, CCNO, ULK4P2, FAM57A, SCARA3, CERS1, BEND5, HAPLN3, DNMBP, KIAA1522, PIR, GTF3C5 ECHDC3, ICAM1, RAB3A, SDHA, C9orf116, MKI67, LMTK3, MCM10, ADM2, HSD17B14, LOC102724002, KCNH2, PRAME, KIAA1279, LOC101929974, ARHGAP21, SULT2B1, ADCY6, GBF1, TUBGCP2, CD19, SPIRE2, SH3PXD2B, AADAT, FOXC1, ZBED3, TSKU, NRARP, AMIGO2, PCBD1, TCAM1P, FAM57B, LOC101929021, PCK2, CCDC127, MGMT, C6orf147, TGFB1I1, DPP4, ALX4, TACC2, WLS, PACSIN3, NAPA-AS1, LINC00999, BAIAP3, ANKH, VDAC2, TAF3, ECHS1, EFNA3, CORO6, TCTN2, HPS1, DNAJB12, SPIB, SLC29A3, PHGDH, PTMS, TMEM91, SEC24C, HGD, MSS51, TEAD3, LARP4B, ZCCHC24, ARHGEF16, FOXO6, FBXO18, PPRC1, CCDC78, RHBDL1, SPINT1, STON2, NUDT8, NEBL, EPAS1, FAM178A, PI4K2A, SNED1, STAM, PLOD2, TM7SF2, FGD1, PCDHB6, CCNB3, MCMDC2, EDRF1, NRM, PPIF, ATF5, BRD9, B3GALT4, NET1, TMEM169, RPH3AL, DROSHA, RBMS2, POLR3A, TRIP13, LPHN1, ZMIZ1, RP11-344B5.2, HNRNPF, HSD17B7P2, SLIT1, LOC648987, ACTR1A, CCT5, S1PR5, WDFY4, GRK5, SREBF1, STXBP5L, VARS2, GAB2, ZFP36L1, CPNE7, HSPA2, NAT8L, DOK4, IGF1R, KHK, KIRREL2, COMTD1, ZNF488, CASC10, QRICH2, RBM17, LSS, PAX8, PKN3, HELLS, FN3K, CDC42EP1, NFIX, BMS1, STOX1, SEMA4B, SUPV3L1, FAM198A, RCOR2, PDCD4, PPAP2A, DDX12P, ACY3, TSPAN10, NUP155, RIBC2, PLCXD1, TP53INP2, GOLPH3, WDR70, BTRC, SVIL, DTX4, DUSP5, ECE1, MRPL43, SKP2, SNHG3, MYRF, ZFYVE27, H2AFY2, NOLC1, SLC25A28, WNK2, NDUFS6, SLC30A3, LOC642846, NEURL1B, ARMC4, SFXN3, VASH2, NOTUM, VCL, LOC100506901, CSTF2T, PRICKLE1, ZNF132, GPR153, ZMYND11, DGCR5, OXER1, VTI1A, PCDHGC3, MORC4, EIF3A, PDCD11, SLC38A1, MC1R, CBS, AC002454.1, PDCD6, B4GALNT1, RPP38, SUGT1P1, NEDD4L, PROCA1, SH3PXD2A, JAG2, FGFR3, TMEM191B, SEPHS1, LOC100505761, C21orf58, FADS1, TET1, GBGT1, KAT6B, KIFC2, TAF5, CASP7, PELI3, PP7080, ATN1, KIAA1598, FAM115A, NKX3-2, CHCHD10, GPSM1, LRP4, CDT1, EIF4EBP2, AASS, ABCC6P1, ABCD2, ADAMTS14, AGAP4, AGAP9, AIFM2, DB1 / 147901903.2 10 AKR1C1, AKR1E2, ANK3, ANKRD33B, ANO6, APBB1IP, ARHGAP19, ARNTL2, ARSG, ARTN, ASCC1, ASUN, BAG3, BEND4, BEX5, BLNK, BTAF1, C10orf10, C10orf12, C10orf76, C10orf91, C15orf38, C2CD4C, C2CD5, C3orf18, CALHM2, CAMK1D, CAPRIN2, CDH2, CDHR1, CEL, CEP72, CES3, CES4A, CHST3, CLIC5, CMAS, CNNM2, CNTN1, COL27A1, COL4A5, CPS1, CRABP1, CTBP2, CUEDC2, CXorf57, DAPK2, DDAH2, DDX11, DDX11-AS1, DENND5B, DHTKD1, DNM1L, DPCD, DPY19L2, DUSP5P1, EBF3, EFEMP2, EGFR, ELK1, EPHB4, FAM155B, FAM175B, FAM21C, FAM45A, FAM53B, FAM84B, FCER2, FGD4, FOXL2, FZD8, GAS1, GPC6, GRIA3, GUCY1B3, GYPE, HDHD3, HES4, HIF1AN, HMGCS1, HMX2, HMX3, HOXB13, HOXB6, HSD17B8, HSH2D, IDE, INPP5A, INPP5F, INPP5J, IPO8, IRAK4, ITPR2, ITPR3, JMJD1C, KAZALD1, KCNQ5, KCNS3, KIAA1324, KIF11, KLHL42, KLLN, KRAS, KREMEN2, LAT, LDB1, LGALS3BP, LINC00477, LIPE, LOC100288152, LOC100506688, LOC100506691, LOC100507487, LOC101927104, LOC101927799, LOC101928913, LOC102723337, LOC102724472, LPCAT1, LRMP, LRRC10B, LRRC20, LRRC27, LTK, LY6G5C, LZTS2, MAP2K6, MASTL, MCIDAS, MCMBP, MDGA2, METTL12, METTL20, MMS19, MPPED2, MRPS16, MRPS35, MSX1, MX1, NDUFB8, NEURL1, NEUROG3, NFKB2, NIM1K, NKD2, NLGN2, NNT, NNT-AS1, NT5DC2, NUDT13, OGDHL, OVOL2, OXCT1, P2RX7, P4HA1, PABPC1L, PANK1, PAOX, PAPD7, PAPSS2, PCDHB13, PCDHB14, PCED1B, PCED1B-AS1, PCSK5, PDLIM1, PEAR1, PFKP, PGAM1, PGAM4, PI15, PITX1, PLEKHA8P1, PLEKHO1, PPFIBP1, PPP2R2D, PPP3CB, PRTFDC1, PSTPIP2, PTENP1, PVRL3, PWWP2B, PXDC1, RNF208, ROBO1, RP11-184I16.4, RP11-53O19.1, RP11-96H19.1, RPAP3, RTN1, SAMD11, SAMD8, SCAF11, SCD5, SDHAP3, SEC14L2, SEC31B, SEC61A2, SECTM1, SFMBT2, SFXN2, SHANK3, SHISA3, SHISA7, SIDT1, SKIDA1, SLA2, SLC12A7, SLC16A6, SLC16A9, SLC4A11, SLITRK5, SMAD1, SNHG12, SNORA61, SNORD104, SOX1, SPEF2, SRRM3, SUFU, TARS, TCF7, TEX15, TGFBR3L, THBD, TIAL1, TLX3, TM7SF3, TMEM180, TMEM191C, TMEM255A, TMEM63C, TRIM72, TUBB3, TYSND1, UGT3A2, ULK2, UNC13D, USP54, VENTX, VIM, XPNPEP1, YARS2, YPEL3, ZDHHC16, ZDHHC6, ZNF43, ZNF438, ZNF503, ZNF503-AS2, ZNF511, ZNF574, ZNF622, ZNF726, ZNF99, ZWINT, ADM, ALDOC, BNIP3, CA3, CD209, CSMD3, DDIT4, FCGR2B, FCGR2C, FIGN, GLIS2, SHISA8, SOX5, TBC1D30, TLE6, TLX1, VAT1L, VEGFA, ANXA4, APLN, C1QL4, CCDC102A, CHDH, EGLN3, ENO2, FADS2, HK2, HSPA, IL17RB, KLF2, LAMC, LINC00263, LOC101928092, DB1 / 147901903.2 11 LOC102724908, MIR210HG, NRTN, PFKFB4, SCD, SLC4A3, SLC6A8, ZNF215, and ZNF395 in the subject, optionally the compound decreases the expression of one or more IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3 in the subject. In one embodiment, upon administration to the subject, Compound 8 increases the expression of one or more IRAK1 / 4-associated genes selected from: PLS3, HSBP1L1, CDC42BPA, PPP2R3A, GNG12, PENK, STC2, DNAJC22, SH3D19, GABRD, RAVER2, ARHGEF26, APBB2, BAI2, DPEP1, LGI2, PIP5K1A, SOX18, BMP4, TMC4, KCNIP3, CCNO, ULK4P2, FAM57A, SCARA3, CERS1, BEND5, HAPLN3, DNMBP, KIAA1522, PIR, GTF3C5 ECHDC3, ICAM1, RAB3A, SDHA, C9orf116, MKI67, LMTK3, MCM10, ADM2, HSD17B14, LOC102724002, KCNH2, PRAME, KIAA1279, LOC101929974, ARHGAP21, SULT2B1, ADCY6, GBF1, TUBGCP2, CD19, SPIRE2, SH3PXD2B, AADAT, FOXC1, ZBED3, TSKU, NRARP, AMIGO2, PCBD1, TCAM1P, FAM57B, LOC101929021, PCK2, CCDC127, MGMT, C6orf147, TGFB1I1, DPP4, ALX4, TACC2, WLS, PACSIN3, NAPA-AS1, LINC00999, BAIAP3, ANKH, VDAC2, TAF3, ECHS1, EFNA3, CORO6, TCTN2, HPS1, DNAJB12, SPIB, SLC29A3, PHGDH, PTMS, TMEM91, SEC24C, HGD, MSS51, TEAD3, LARP4B, ZCCHC24, ARHGEF16, FOXO6, FBXO18, PPRC1, CCDC78, RHBDL1, SPINT1, STON2, NUDT8, NEBL, EPAS1, FAM178A, PI4K2A, SNED1, STAM, PLOD2, TM7SF2, FGD1, PCDHB6, CCNB3, MCMDC2, EDRF1, NRM, PPIF, ATF5, BRD9, B3GALT4, NET1, TMEM169, RPH3AL, DROSHA, RBMS2, POLR3A, TRIP13, LPHN1, ZMIZ1, RP11-344B5.2, HNRNPF, HSD17B7P2, SLIT1, LOC648987, ACTR1A, CCT5, S1PR5, WDFY4, GRK5, SREBF1, STXBP5L, VARS2, GAB2, ZFP36L1, CPNE7, HSPA2, NAT8L, DOK4, IGF1R, KHK, KIRREL2, COMTD1, ZNF488, CASC10, QRICH2, RBM17, LSS, PAX8, PKN3, HELLS, FN3K, CDC42EP1, NFIX, BMS1, STOX1, SEMA4B, SUPV3L1, FAM198A, RCOR2, PDCD4, PPAP2A, DDX12P, ACY3, TSPAN10, NUP155, RIBC2, PLCXD1, TP53INP2, GOLPH3, WDR70, BTRC, SVIL, DTX4, DUSP5, ECE1, MRPL43, SKP2, SNHG3, MYRF, ZFYVE27, H2AFY2, NOLC1, SLC25A28, WNK2, NDUFS6, SLC30A3, LOC642846, NEURL1B, DB1 / 147901903.2 12 ARMC4, SFXN3, VASH2, NOTUM, VCL, LOC100506901, CSTF2T, PRICKLE1, ZNF132, GPR153, ZMYND11, DGCR5, OXER1, VTI1A, PCDHGC3, MORC4, EIF3A, PDCD11, SLC38A1, MC1R, CBS, AC002454.1, PDCD6, B4GALNT1, RPP38, SUGT1P1, NEDD4L, PROCA1, SH3PXD2A, JAG2, FGFR3, TMEM191B, SEPHS1, LOC100505761, C21orf58, FADS1, TET1, GBGT1, KAT6B, KIFC2, TAF5, CASP7, PELI3, PP7080, ATN1, KIAA1598, FAM115A, NKX3-2, CHCHD10, GPSM1, LRP4, CDT1, EIF4EBP2, AASS, ABCC6P1, ABCD2, ADAMTS14, AGAP4, AGAP9, AIFM2, AKR1C1, AKR1E2, ANK3, ANKRD33B, ANO6, APBB1IP, ARHGAP19, ARNTL2, ARSG, ARTN, ASCC1, ASUN, BAG3, BEND4, BEX5, BLNK, BTAF1, C10orf10, C10orf12, C10orf76, C10orf91, C15orf38, C2CD4C, C2CD5, C3orf18, CALHM2, CAMK1D, CAPRIN2, CDH2, CDHR1, CEL, CEP72, CES3, CES4A, CHST3, CLIC5, CMAS, CNNM2, CNTN1, COL27A1, COL4A5, CPS1, CRABP1, CTBP2, CUEDC2, CXorf57, DAPK2, DDAH2, DDX11, DDX11-AS1, DENND5B, DHTKD1, DNM1L, DPCD, DPY19L2, DUSP5P1, EBF3, EFEMP2, EGFR, ELK1, EPHB4, FAM155B, FAM175B, FAM21C, FAM45A, FAM53B, FAM84B, FCER2, FGD4, FOXL2, FZD8, GAS1, GPC6, GRIA3, GUCY1B3, GYPE, HDHD3, HES4, HIF1AN, HMGCS1, HMX2, HMX3, HOXB13, HOXB6, HSD17B8, HSH2D, IDE, INPP5A, INPP5F, INPP5J, IPO8, IRAK4, ITPR2, ITPR3, JMJD1C, KAZALD1, KCNQ5, KCNS3, KIAA1324, KIF11, KLHL42, KLLN, KRAS, KREMEN2, LAT, LDB1, LGALS3BP, LINC00477, LIPE, LOC100288152, LOC100506688, LOC100506691, LOC100507487, LOC101927104, LOC101927799, LOC101928913, LOC102723337, LOC102724472, LPCAT1, LRMP, LRRC10B, LRRC20, LRRC27, LTK, LY6G5C, LZTS2, MAP2K6, MASTL, MCIDAS, MCMBP, MDGA2, METTL12, METTL20, MMS19, MPPED2, MRPS16, MRPS35, MSX1, MX1, NDUFB8, NEURL1, NEUROG3, NFKB2, NIM1K, NKD2, NLGN2, NNT, NNT-AS1, NT5DC2, NUDT13, OGDHL, OVOL2, OXCT1, P2RX7, P4HA1, PABPC1L, PANK1, PAOX, PAPD7, PAPSS2, PCDHB13, PCDHB14, PCED1B, PCED1B-AS1, PCSK5, PDLIM1, PEAR1, PFKP, PGAM1, PGAM4, PI15, PITX1, PLEKHA8P1, PLEKHO1, PPFIBP1, PPP2R2D, PPP3CB, PRTFDC1, PSTPIP2, PTENP1, PVRL3, PWWP2B, PXDC1, RNF208, ROBO1, RP11-184I16.4, RP11-53O19.1, RP11-96H19.1, RPAP3, RTN1, SAMD11, SAMD8, SCAF11, SCD5, SDHAP3, SEC14L2, SEC31B, SEC61A2, SECTM1, SFMBT2, SFXN2, SHANK3, SHISA3, SHISA7, SIDT1, SKIDA1, SLA2, SLC12A7, SLC16A6, SLC16A9, SLC4A11, SLITRK5, SMAD1, SNHG12, SNORA61, SNORD104, SOX1, SPEF2, SRRM3, SUFU, TARS, TCF7, TEX15, TGFBR3L, DB1 / 147901903.2 13 THBD, TIAL1, TLX3, TM7SF3, TMEM180, TMEM191C, TMEM255A, TMEM63C, TRIM72, TUBB3, TYSND1, UGT3A2, ULK2, UNC13D, USP54, VENTX, VIM, XPNPEP1, YARS2, YPEL3, ZDHHC16, ZDHHC6, ZNF43, ZNF438, ZNF503, ZNF503-AS2, ZNF511, ZNF574, ZNF622, ZNF726, ZNF99, ZWINT, ADM, ALDOC, BNIP3, CA3, CD209, CSMD3, DDIT4, FCGR2B, FCGR2C, FIGN, GLIS2, SHISA8, SOX5, TBC1D30, TLE6, TLX1, VAT1L, VEGFA, ANXA4, APLN, C1QL4, CCDC102A, CHDH, EGLN3, ENO2, FADS2, HK2, HSPA7, IL17RB, KLF2, LAMC, LINC00263, LOC101928092, LOC102724908, MIR210HG, NRTN, PFKFB4, SCD, SLC4A3, SLC6A8, ZNF215, and ZNF395 in the subject, optionally wherein the compound increases the expression of one or more IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3 in the subject. In one embodiment, the subject in need thereof has elevated expression of one or more NFκB- associated genes, and / or decreased expression of one or more NFκB-associated genes. In one embodiment, the subject in need thereof has elevated expression of one or more NFκB- associated genes compared to a healthy control subject, and / or decreased expression of one or more NFκB-associated genes compared to a healthy control subject. In one embodiment, the subject in need thereof has elevated expression of one or more NFκB-associated genes selected from: A4, ABCA1, ABCB1, ABCB4, ABCB9, ABCC6, ABCG5, ABCG8, ADAM19, ADH1A, ADORA1, ADORA2A, ADRA2B. AFP, AGER, AGT, AHCTF1, AICDA, AKR1C1, ALOX12, ALOX5, AMACR, AMH, ANGPT1, APOBEC2, APOC3, APOD, APOE, AQP4, AR, ARFRP1, ART1, ASPH, ASS1, ATP1A2, B2M, BACE1, BAX, BCL2, BCL2A1, BCL2L1, BCL2L11, BCL3, BDKRB1, BDKRB1, BDNF, BGN, BLIMP1 / PRDM1, BLNK, BLR1, BMI1, BMP2, BMP4, BNIP3, BRCA2, BTK, C3, C4A, C4BPA, C69, CALCB, CASP4, CAV1, CCL1, CCL15, CCL17, CCL19, CCL2, CCL20, CCL22, CCL23, CCL28, CCL3, CCL4, CCL5, CCND1, CCND2, CCND3, CCR5, CCR7, CD209, CD274, CD38, CD3G, CD40, CD40LG, CD44, CD48, CD54, CD80, CD83, CD86, CDK6, CDKN1A, CDX1, CEBPD, CFB, CFLAR, CGM3, CHI3L1, CIDEA, CLDN2, COL1A2, CR2, CREB3, CRP, CSF1, CSF2, CSF3, CTSB, DB1 / 147901903.2 14 CTSL1, CXCL1, CXCL10, CXCL11, CXCL3, CXCL5, CXCL6, CXCL9, CYP19A1, CYP27B1, CYP2C11, CYP2E1, CYP7B1, DCTN4, DEFB2, DIO2, DMP1, DNASE1L2, DPYD, DUSP1, E2F3, EBI3, EDN1, EGFR, EGR1, ELF3, ENG, ENO2, EPHA1, EPO, ERBB2, ERVWE1, F11R, F3, F8, FABP6, FAM148A, FAS, FASLG, FCER2. FCER2 / CD23, FCGRT, FGF8, FN1, FOS, FSTL3, FTH1, G6PC, G6PD, GAD1, GADD45B, GATA3, GBP1, GCLC, GCLM, GCNT1, GJB1, GNAI2, GNB2L1, GNRH2, GRIN1, GRIN2A, GRM2, GRO-beta, GRO-gamma, GSTP1, GUCY1A2, GZMB, HAMP, HAS1, HBE1, HBZ, HGF, HIF1A, HLA-B, HLA-G, HMGN1, HMOX1, HOXA9, HPSE, HSD11B2, HSD17B8, HSP90AA1, ICOS, IDO1, IER2, IER3, IFI44L, IFNB, IFNG, IGFBP1, IGFBP2, IGHE, IGHG1, IGHG2, IGHG4, IGKC, Iigp1, IL10, IL11, IL12A, IL12B, IL13, IL15, IL17, IL1A, IL1B, IL1RN, IL2, IL23A, IL27, IL2RA, IL6, IL8, IL8RA, IL8RB, IL9, INHBA, IRF1, IRF2, IRF4, IRF7, JMJD3, JUNB, KC, KCNK5, KCNN2, KISS1, KITLG, KLF10, KLK3, KLRA1, KRT15, KRT3, KRT5, KRT6B, LAMB2, LBP, LCN2, LEF1, LGALS3, LIPG, LTA, LTB, LTF, LYZ, MADCAM1, MAP4K1, MBP, MDK, MMP1, MMP3, MMP9, MT3, MTHFR, MUC2, MX1, MYB, MYC, MYLK, MYOZ1, NCAM, NFKB1, NFKB2, NFKBIA, NFKBIE, NFKBIZ, NGFB, NK4, NLRP2, NOD2, NOS1, NOS2A, NOX1, NPY1R, NQO1, NR3C1, NR4A2, NRG1, NUAK2, OLR1, OPN1SW, OPRD1, OPRM1, ORM1, Osterix, OXTR, PAFAH2, PAX8, PDE7A, PDGFB, PDYN, PENK, PGK1, PGLYRP1, PGR, PI3KAP1, PIGF, pIgR, PIK3CA, PIM1, PLA2, PLAU, PLCD1, PLK3, POMC, PPARGC1B, PPP5C, PRF1, PRKACA, PRKCD, PRL, PSMB9, PSME1, PSME2, PTAFR,, PTEN, PTGDS, PTGES, PTGIS, PTGS2, PTHLH, PTPN1, PTPN13, PTS, PTX3, PYCARD, RAG1, RAG2, RBBP4, Rdh1, Rdh7, REL, RELB, REV3L, RIPK2, S100A10, S100A4, S100A6, SAA1, SAA2, SAA, SAT1, SCNN1A, SDC4, SELE, SELP, SELS, SENP2, SERPINA1, SERPINA2, SERPINA3, SERPINB1, SERPINE1, PAI-1, SERPINE2, SH3BGRL, SKALP, PI3, SKP2, SLC11A2, SLC16A1, SLC3A2, SLC6A6, Slfn2, SNAI1, SOD1, SOD2, SOX9, SPATA19, SPI1, SPP1, ST6GAL1, ST8SIA1, STAT5A, SUPV3L1, TACR1, TAP1, TAPBP, TCRB, TERT, TF, TFEC, TFF3, TFPI2, TGM1, TGM2, THBS1, THBS2, TICAM1, TIFA, TLR2, TLR9, TNC, TN, TNFAIP2, TNFAIP3, TNFRSF1B, TNFRSF4, TNFRSF9, TNFSF10, TNFSF13B, TNFSF13B, TNFSF15, TNIP1, TNIP3, TP53, TRAF1, TRAF2, TREM1, TRPC1, TWIST1, UBE2M, UCP2, UGCGL1, UPK1B, UPP1, VCAM1, VEGFC, VIM, VPS53, WNT10B, WT1, XDH, XIAP, YY1, and ZNF366. In one embodiment, the subject in need thereof has decreased expression of one or more NFκB- DB1 / 147901903.2 15 associated genes selected from: A4, ABCA1, ABCB1, ABCB4, ABCB9, ABCC6, ABCG5, ABCG8, ADAM19, ADH1A, ADORA1, ADORA2A, ADRA2B. AFP, AGER, AGT, AHCTF1, AICDA, AKR1C1, ALOX12, ALOX5, AMACR, AMH, ANGPT1, APOBEC2, APOC3, APOD, APOE, AQP4, AR, ARFRP1, ART1, ASPH, ASS1, ATP1A2, B2M, BACE1, BAX, BCL2, BCL2A1, BCL2L1, BCL2L11, BCL3, BDKRB1, BDKRB1, BDNF, BGN, BLIMP1 / PRDM1, BLNK, BLR1, BMI1, BMP2, BMP4, BNIP3, BRCA2, BTK, C3, C4A, C4BPA, C69, CALCB, CASP4, CAV1, CCL1, CCL15, CCL17, CCL19, CCL2, CCL20, CCL22, CCL23, CCL28, CCL3, CCL4, CCL5, CCND1, CCND2, CCND3, CCR5, CCR7, CD209, CD274, CD38, CD3G, CD40, CD40LG, CD44, CD48, CD54, CD80, CD83, CD86, CDK6, CDKN1A, CDX1, CEBPD, CFB, CFLAR, CGM3, CHI3L1, CIDEA, CLDN2, COL1A2, CR2, CREB3, CRP, CSF1, CSF2, CSF3, CTSB, CTSL1, CXCL1, CXCL10, CXCL11, CXCL3, CXCL5, CXCL6, CXCL9, CYP19A1, CYP27B1, CYP2C11, CYP2E1, CYP7B1, DCTN4, DEFB2, DIO2, DMP1, DNASE1L2, DPYD, DUSP1, E2F3, EBI3, EDN1, EGFR, EGR1, ELF3, ENG, ENO2, EPHA1, EPO, ERBB2, ERVWE1, F11R, F3, F8, FABP6, FAM148A, FAS, FASLG, FCER2. FCER2 / CD23, FCGRT, FGF8, FN1, FOS, FSTL3, FTH1, G6PC, G6PD, GAD1, GADD45B, GATA3, GBP1, GCLC, GCLM, GCNT1, GJB1, GNAI2, GNB2L1, GNRH2, GRIN1, GRIN2A, GRM2, GRO-beta, GRO-gamma, GSTP1, GUCY1A2, GZMB, HAMP, HAS1, HBE1, HBZ, HGF, HIF1A, HLA-B, HLA-G, HMGN1, HMOX1, HOXA9, HPSE, HSD11B2, HSD17B8, HSP90AA1, ICOS, IDO1, IER2, IER3, IFI44L, IFNB, IFNG, IGFBP1, IGFBP2, IGHE, IGHG1, IGHG2, IGHG4, IGKC, Iigp1, IL10, IL11, IL12A, IL12B, IL13, IL15, IL17, IL1A, IL1B, IL1RN, IL2, IL23A, IL27, IL2RA, IL6, IL8, IL8RA, IL8RB, IL9, INHBA, IRF1, IRF2, IRF4, IRF7, JMJD3, JUNB, KC, KCNK5, KCNN2, KISS1, KITLG, KLF10, KLK3, KLRA1, KRT15, KRT3, KRT5, KRT6B, LAMB2, LBP, LCN2, LEF1, LGALS3, LIPG, LTA, LTB, LTF, LYZ, MADCAM1, MAP4K1, MBP, MDK, MMP1, MMP3, MMP9, MT3, MTHFR, MUC2, MX1, MYB, MYC, MYLK, MYOZ1, NCAM, NFKB1, NFKB2, NFKBIA, NFKBIE, NFKBIZ, NGFB, NK4, NLRP2, NOD2, NOS1, NOS2A, NOX1, NPY1R, NQO1, NR3C1, NR4A2, NRG1, NUAK2, OLR1, OPN1SW, OPRD1, OPRM1, ORM1, Osterix, OXTR, PAFAH2, PAX8, PDE7A, PDGFB, PDYN, PENK, PGK1, PGLYRP1, PGR, PI3KAP1, PIGF, pIgR, PIK3CA, PIM1, PLA2, PLAU, PLCD1, PLK3, POMC, PPARGC1B, PPP5C, PRF1, PRKACA, PRKCD, PRL, PSMB9, PSME1, PSME2, PTAFR,, PTEN, PTGDS, PTGES, PTGIS, PTGS2, PTHLH, PTPN1, PTPN13, PTS, PTX3, PYCARD, RAG1, RAG2, RBBP4, Rdh1, Rdh7, REL, RELB, DB1 / 147901903.2 16 REV3L, RIPK2, S100A10, S100A4, S100A6, SAA1, SAA2, SAA, SAT1, SCNN1A, SDC4, SELE, SELP, SELS, SENP2, SERPINA1, SERPINA2, SERPINA3, SERPINB1, SERPINE1, PAI-1, SERPINE2, SH3BGRL, SKALP, PI3, SKP2, SLC11A2, SLC16A1, SLC3A2, SLC6A6, Slfn2, SNAI1, SOD1, SOD2, SOX9, SPATA19, SPI1, SPP1, ST6GAL1, ST8SIA1, STAT5A, SUPV3L1, TACR1, TAP1, TAPBP, TCRB, TERT, TF, TFEC, TFF3, TFPI2, TGM1, TGM2, THBS1, THBS2, TICAM1, TIFA, TLR2, TLR9, TNC, TN, TNFAIP2, TNFAIP3, TNFRSF1B, TNFRSF4, TNFRSF9, TNFSF10, TNFSF13B, TNFSF13B, TNFSF15, TNIP1, TNIP3, TP53, TRAF1, TRAF2, TREM1, TRPC1, TWIST1, UBE2M, UCP2, UGCGL1, UPK1B, UPP1, VCAM1, VEGFC, VIM, VPS53, WNT10B, WT1, XDH, XIAP, YY1, and ZNF366. In one embodiment, upon administration to the subject, Compound 8 decreases the expression of one or more NFκB-associated genes found to be elevated in the subject, and / or increases the expression of one or more NFκB-associated genes found to be decreased in the subject. In one embodiment, the administration of Compound 8 decreases the expression of the one or more NFκB-associated genes found to be elevated in the subject before the administration of Compound 8, and / or increases the expression of the one or more NFκB-associated genes found to be decreased in the subject before the administration of Compound 8. In one embodiment, Compound 8 decreases the expression of one or more NFκB-associated genes found to be elevated in the subject compared to a healthy control subject, and / or increases the expression of one or more NFκB- associated genes found to be decreased in the subject compared to a healthy control subject. In one embodiment, upon administration to the subject, Compound 8 decreases the expression of one or more NFκB-associated genes selected from: A4, ABCA1, ABCB1, ABCB4, ABCB9, ABCC6, ABCG5, ABCG8, ADAM19, ADH1A, ADORA1, ADORA2A, ADRA2B. AFP, AGER, AGT, AHCTF1, AICDA, AKR1C1, ALOX12, ALOX5, AMACR, AMH, ANGPT1, APOBEC2, APOC3, APOD, APOE, AQP4, AR, ARFRP1, ART1, ASPH, ASS1, ATP1A2, B2M, BACE1, BAX, BCL2, BCL2A1, BCL2L1, BCL2L11, BCL3, BDKRB1, BDKRB1, BDNF, BGN, BLIMP1 / PRDM1, BLNK, BLR1, BMI1, BMP2, BMP4, BNIP3, BRCA2, BTK, C3, C4A, C4BPA, C69, CALCB, CASP4, CAV1, CCL1, CCL15, CCL17, CCL19, CCL2, CCL20, CCL22, CCL23, CCL28, CCL3, CCL4, CCL5, CCND1, CCND2, CCND3, CCR5, CCR7, CD209, CD274, CD38, CD3G, CD40, CD40LG, CD44, CD48, CD54, CD80, CD83, CD86, CDK6, CDKN1A, CDX1, CEBPD, CFB, CFLAR, CGM3, CHI3L1, CIDEA, CLDN2, COL1A2, CR2, CREB3, CRP, CSF1, CSF2, CSF3, CTSB, CTSL1, CXCL1, CXCL10, DB1 / 147901903.2 17 CXCL11, CXCL3, CXCL5, CXCL6, CXCL9, CYP19A1, CYP27B1, CYP2C11, CYP2E1, CYP7B1, DCTN4, DEFB2, DIO2, DMP1, DNASE1L2, DPYD, DUSP1, E2F3, EBI3, EDN1, EGFR, EGR1, ELF3, ENG, ENO2, EPHA1, EPO, ERBB2, ERVWE1, F11R, F3, F8, FABP6, FAM148A, FAS, FASLG, FCER2. FCER2 / CD23, FCGRT, FGF8, FN1, FOS, FSTL3, FTH1, G6PC, G6PD, GAD1, GADD45B, GATA3, GBP1, GCLC, GCLM, GCNT1, GJB1, GNAI2, GNB2L1, GNRH2, GRIN1, GRIN2A, GRM2, GRO-beta, GRO-gamma, GSTP1, GUCY1A2, GZMB, HAMP, HAS1, HBE1, HBZ, HGF, HIF1A, HLA-B, HLA-G, HMGN1, HMOX1, HOXA9, HPSE, HSD11B2, HSD17B8, HSP90AA1, ICOS, IDO1, IER2, IER3, IFI44L, IFNB, IFNG, IGFBP1, IGFBP2, IGHE, IGHG1, IGHG2, IGHG4, IGKC, Iigp1, IL10, IL11, IL12A, IL12B, IL13, IL15, IL17, IL1A, IL1B, IL1RN, IL2, IL23A, IL27, IL2RA, IL6, IL8, IL8RA, IL8RB, IL9, INHBA, IRF1, IRF2, IRF4, IRF7, JMJD3, JUNB, KC, KCNK5, KCNN2, KISS1, KITLG, KLF10, KLK3, KLRA1, KRT15, KRT3, KRT5, KRT6B, LAMB2, LBP, LCN2, LEF1, LGALS3, LIPG, LTA, LTB, LTF, LYZ, MADCAM1, MAP4K1, MBP, MDK, MMP1, MMP3, MMP9, MT3, MTHFR, MUC2, MX1, MYB, MYC, MYLK, MYOZ1, NCAM, NFKB1, NFKB2, NFKBIA, NFKBIE, NFKBIZ, NGFB, NK4, NLRP2, NOD2, NOS1, NOS2A, NOX1, NPY1R, NQO1, NR3C1, NR4A2, NRG1, NUAK2, OLR1, OPN1SW, OPRD1, OPRM1, ORM1, Osterix, OXTR, PAFAH2, PAX8, PDE7A, PDGFB, PDYN, PENK, PGK1, PGLYRP1, PGR, PI3KAP1, PIGF, pIgR, PIK3CA, PIM1, PLA2, PLAU, PLCD1, PLK3, POMC, PPARGC1B, PPP5C, PRF1, PRKACA, PRKCD, PRL, PSMB9, PSME1, PSME2, PTAFR,, PTEN, PTGDS, PTGES, PTGIS, PTGS2, PTHLH, PTPN1, PTPN13, PTS, PTX3, PYCARD, RAG1, RAG2, RBBP4, Rdh1, Rdh7, REL, RELB, REV3L, RIPK2, S100A10, S100A4, S100A6, SAA1, SAA2, SAA, SAT1, SCNN1A, SDC4, SELE, SELP, SELS, SENP2, SERPINA1, SERPINA2, SERPINA3, SERPINB1, SERPINE1, PAI-1, SERPINE2, SH3BGRL, SKALP, PI3, SKP2, SLC11A2, SLC16A1, SLC3A2, SLC6A6, Slfn2, SNAI1, SOD1, SOD2, SOX9, SPATA19, SPI1, SPP1, ST6GAL1, ST8SIA1, STAT5A, SUPV3L1, TACR1, TAP1, TAPBP, TCRB, TERT, TF, TFEC, TFF3, TFPI2, TGM1, TGM2, THBS1, THBS2, TICAM1, TIFA, TLR2, TLR9, TNC, TN, TNFAIP2, TNFAIP3, TNFRSF1B, TNFRSF4, TNFRSF9, TNFSF10, TNFSF13B, TNFSF13B, TNFSF15, TNIP1, TNIP3, TP53, TRAF1, TRAF2, TREM1, TRPC1, TWIST1, UBE2M, UCP2, UGCGL1, UPK1B, UPP1, VCAM1, VEGFC, VIM, VPS53, WNT10B, WT1, XDH, XIAP, YY1, and ZNF366 in the subject. In one embodiment, upon administration to the subject, Compound 8 increases the expression of one or DB1 / 147901903.2 18 more NFκB-associated genes selected from: A4, ABCA1, ABCB1, ABCB4, ABCB9, ABCC6, ABCG5, ABCG8, ADAM19, ADH1A, ADORA1, ADORA2A, ADRA2B. AFP, AGER, AGT, AHCTF1, AICDA, AKR1C1, ALOX12, ALOX5, AMACR, AMH, ANGPT1, APOBEC2, APOC3, APOD, APOE, AQP4, AR, ARFRP1, ART1, ASPH, ASS1, ATP1A2, B2M, BACE1, BAX, BCL2, BCL2A1, BCL2L1, BCL2L11, BCL3, BDKRB1, BDKRB1, BDNF, BGN, BLIMP1 / PRDM1, BLNK, BLR1, BMI1, BMP2, BMP4, BNIP3, BRCA2, BTK, C3, C4A, C4BPA, C69, CALCB, CASP4, CAV1, CCL1, CCL15, CCL17, CCL19, CCL2, CCL20, CCL22, CCL23, CCL28, CCL3, CCL4, CCL5, CCND1, CCND2, CCND3, CCR5, CCR7, CD209, CD274, CD38, CD3G, CD40, CD40LG, CD44, CD48, CD54, CD80, CD83, CD86, CDK6, CDKN1A, CDX1, CEBPD, CFB, CFLAR, CGM3, CHI3L1, CIDEA, CLDN2, COL1A2, CR2, CREB3, CRP, CSF1, CSF2, CSF3, CTSB, CTSL1, CXCL1, CXCL10, CXCL11, CXCL3, CXCL5, CXCL6, CXCL9, CYP19A1, CYP27B1, CYP2C11, CYP2E1, CYP7B1, DCTN4, DEFB2, DIO2, DMP1, DNASE1L2, DPYD, DUSP1, E2F3, EBI3, EDN1, EGFR, EGR1, ELF3, ENG, ENO2, EPHA1, EPO, ERBB2, ERVWE1, F11R, F3, F8, FABP6, FAM148A, FAS, FASLG, FCER2. FCER2 / CD23, FCGRT, FGF8, FN1, FOS, FSTL3, FTH1, G6PC, G6PD, GAD1, GADD45B, GATA3, GBP1, GCLC, GCLM, GCNT1, GJB1, GNAI2, GNB2L1, GNRH2, GRIN1, GRIN2A, GRM2, GRO-beta, GRO-gamma, GSTP1, GUCY1A2, GZMB, HAMP, HAS1, HBE1, HBZ, HGF, HIF1A, HLA-B, HLA-G, HMGN1, HMOX1, HOXA9, HPSE, HSD11B2, HSD17B8, HSP90AA1, ICOS, IDO1, IER2, IER3, IFI44L, IFNB, IFNG, IGFBP1, IGFBP2, IGHE, IGHG1, IGHG2, IGHG4, IGKC, Iigp1, IL10, IL11, IL12A, IL12B, IL13, IL15, IL17, IL1A, IL1B, IL1RN, IL2, IL23A, IL27, IL2RA, IL6, IL8, IL8RA, IL8RB, IL9, INHBA, IRF1, IRF2, IRF4, IRF7, JMJD3, JUNB, KC, KCNK5, KCNN2, KISS1, KITLG, KLF10, KLK3, KLRA1, KRT15, KRT3, KRT5, KRT6B, LAMB2, LBP, LCN2, LEF1, LGALS3, LIPG, LTA, LTB, LTF, LYZ, MADCAM1, MAP4K1, MBP, MDK, MMP1, MMP3, MMP9, MT3, MTHFR, MUC2, MX1, MYB, MYC, MYLK, MYOZ1, NCAM, NFKB1, NFKB2, NFKBIA, NFKBIE, NFKBIZ, NGFB, NK4, NLRP2, NOD2, NOS1, NOS2A, NOX1, NPY1R, NQO1, NR3C1, NR4A2, NRG1, NUAK2, OLR1, OPN1SW, OPRD1, OPRM1, ORM1, Osterix, OXTR, PAFAH2, PAX8, PDE7A, PDGFB, PDYN, PENK, PGK1, PGLYRP1, PGR, PI3KAP1, PIGF, pIgR, PIK3CA, PIM1, PLA2, PLAU, PLCD1, PLK3, POMC, PPARGC1B, PPP5C, PRF1, PRKACA, PRKCD, PRL, PSMB9, PSME1, PSME2, PTAFR,, PTEN, PTGDS, PTGES, PTGIS, PTGS2, PTHLH, PTPN1, PTPN13, PTS, PTX3, PYCARD, DB1 / 147901903.2 19 RAG1, RAG2, RBBP4, Rdh1, Rdh7, REL, RELB, REV3L, RIPK2, S100A10, S100A4, S100A6, SAA1, SAA2, SAA, SAT1, SCNN1A, SDC4, SELE, SELP, SELS, SENP2, SERPINA1, SERPINA2, SERPINA3, SERPINB1, SERPINE1, PAI-1, SERPINE2, SH3BGRL, SKALP, PI3, SKP2, SLC11A2, SLC16A1, SLC3A2, SLC6A6, Slfn2, SNAI1, SOD1, SOD2, SOX9, SPATA19, SPI1, SPP1, ST6GAL1, ST8SIA1, STAT5A, SUPV3L1, TACR1, TAP1, TAPBP, TCRB, TERT, TF, TFEC, TFF3, TFPI2, TGM1, TGM2, THBS1, THBS2, TICAM1, TIFA, TLR2, TLR9, TNC, TN, TNFAIP2, TNFAIP3, TNFRSF1B, TNFRSF4, TNFRSF9, TNFSF10, TNFSF13B, TNFSF13B, TNFSF15, TNIP1, TNIP3, TP53, TRAF1, TRAF2, TREM1, TRPC1, TWIST1, UBE2M, UCP2, UGCGL1, UPK1B, UPP1, VCAM1, VEGFC, VIM, VPS53, WNT10B, WT1, XDH, XIAP, YY1, and ZNF366 in the subject. In one embodiment, the subject in need thereof has elevated secretion of one or more cytokines, optionally wherein the one or more cytokines are selected from: TNF-α, IL-1 β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, IL-23, GM-CSF, and IFN-γ. In one embodiment, the subject in need thereof has elevated secretion of one or more cytokines compared to a healthy control subject, optionally wherein the one or more cytokines are selected from: TNF-α, IL-1 β, IL-2, IL- 4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, IL-23, GM-CSF, and IFN-γ. In one embodiment, Compound 8 decreases the secretion of one or more cytokines found to be elevated in the subject, optionally wherein the compound decreases the secretion of one or more cytokines selected from: TNF-α, IL-1 β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, IL-23, GM- CSF, and IFN-γ in the subject. In one embodiment, the administration of Compound 8 decreases the expression of the one or more cytokines found to be elevated in the subject before the administration of Compound 8, and / or increases the expression of the one or more cytokines found to be decreased in the subject before the administration of Compound 8. In one embodiment, upon administration to the subject, Compound 8 decreases the expression of one or more cytokines found to be elevated in the subject compared to a healthy control subject, and / or increases the expression of one or more cytokines found to be decreased in the subject compared to a healthy control subject. In yet another aspect, when Compound 8 is used in any of the methods described above, Compound 8 is more effective at inhibiting cancer cell colony formation and / or cancer progenitor cell function when compared to a compound which inhibits IRAK1 without inhibiting IRAK4 or inhibits IRAK4 without inhibiting IRAK1. In one embodiment, Compound 8 DB1 / 147901903.2 20 provides sustained treatment of the inflammatory disease / disorder, AML, or MDS in the subject, optionally wherein the sustained treatment is greater than the treatment provided from a compound which inhibits IRAK1 without inhibiting IRAK4 or inhibits IRAK4 without inhibiting IRAK1. In one embodiment, in any of the methods described above, the administration of Compound 8 comprises parenteral administration, mucosal administration, intravenous administration, subcutaneous administration, topical administration, intradermal administration, oral administration, sublingual administration, intranasal administration, or intramuscular administration; and / or Compound 8 is administered to the subject in an amount of from about 0.005 mg / kg subject body weight to about 1,000 mg / kg subject body weight; and / or Compound 8 is administered to the subject in a dosage of from about 0.35 mg to about 70,000 mg; and / or Compound 8 is administered to the subject daily, every other day, every third day, every fourth day, every fifth day, every sixth day, once a week, twice a month, or once a month. In one embodiment, in any of the methods described above, Compound 8 treats the inflammatory disease or disorder, or the cancer selected from AML and MDS, in the subject during the time period that the compound is administered to the subject. In one embodiment, in any of the methods described above, Compound 8 continues to treat the inflammatory disease or disorder, or the cancer selected from AML and MDS, in the subject after the administration is stopped, optionally wherein Compound 8 continues to treat the inflammatory disease or disorder, or the cancer selected from AML and MDS, in the subject for about 1 day, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, about one week, about two weeks, about three weeks, or about a month after the administration is stopped. In one embodiment, in any of the methods described above, the method further comprises administering to the subject one or more of: a chemotherapy agent, a BCL2 inhibitor, an immune modulator, a BTK inhibitor, a DNA methyltransferase inhibitor / hypomethylating agent, an anthracycline, a histone deacetylase (HDAC) inhibitor, a purine nucleoside analogue (antimetabolite), an isocitrate dehydrogenase 1 or 2 (IDH1 and / or IDH2) inhibitor, an antibody-drug conjugate, an mAbs / immunotherapy, a Plk inhibitor, a MEK inhibitor, a CDK inhibitor, a CDK9 inhibitor, a CDK8 inhibitor, a retinoic acid receptor agonist, a TP53 activator, a CELMoD, a smoothened receptor antagonist, an ERK inhibitor including an ERK2 / MAPK1 or ERK1 / MAPK3 inhibitor, a PI3K inhibitor, an mTOR inhibitor, a steroid or glucocorticoid, a steroid or glucocorticoid receptor modulator, an EZH2 inhibitor, a hedgehog (Hh) inhibitor, a Topoisomerase I inhibitor, a Topoisomerase II inhibitor, DB1 / 147901903.2 21 an aminopeptidase / Leukotriene A4 hydrolase inhibitor, a FLT3 / Axl / ALK inhibitor, a FLT3 / KIT / PDGFR, PKC, and / or KDR inhibitor, a Syk inhibitor, an E-selectin inhibitor, an NEDD8-activator, an MDM2 inhibitor, a PLK1 inhibitor, an Aura A inhibitor, an aurora kinase inhibitor, an EGFR inhibitor, an AuroraB / C / VEGFR1 / 2 / 3 / FLT3 / CSF-1R / Kit / PDGFRA / B inhibitor, an AKT 1, 2, and / or 3 inhibitor, a ABL1 / 2 / SRC / EPHA2 / LCK / YES1 / KIT / PDGFRB / FYN inhibitor, a farnesyltransferase inhibitor, a BRAF / MAP2K1 / MAP2K2 inhibitor, a Menin-KMT2A / MLL inhibitor, and a multikinase inhibitor; optionally comprising administering to the subject at least one of a BCL2 inhibitor, a BTK inhibitor, a glucocorticoid, a CDK inhibitor, and a DNA methyltransferase inhibitor. In one embodiment, the BCL2 inhibitor is venetoclax or a pharmaceutically acceptable salt thereof; and / or the BTK inhibitor is ibrutinib or a pharmaceutically acceptable salt thereof, or acalabrutinib or a pharmaceutically acceptable salt thereof; and / or the glucocorticoid is selected from dexamethasone, methylprednisolone, prednisolone or a pharmaceutically acceptable salt of any one thereof; and / or the CDK inhibitor is selected from CDK4 / 6 inhibitor Palbociclib, CDK7 inhibitor THZ1, and / or CDK9 inhibitors BAY1251152 and Atuveciclib, or a pharmaceutically acceptable salt of any one thereof; and / or the DNA methyltransferase inhibitor is azacitidine or a pharmaceutically acceptable salt thereof. In one embodiment, the combination of Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, and venetoclax, or a pharmaceutically acceptable salt thereof, increases survival of the subject; optionally wherein the combination of Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, and venetoclax, or a pharmaceutically acceptable salt thereof, increases survival of the subject compared to a subject administered either Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, or venetoclax, or a pharmaceutically acceptable salt thereof; optionally wherein the combination of Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, and venetoclax, or a pharmaceutically acceptable salt thereof, increases survival of the subject by about 10% to 200%, about 10% to 175%, about 20% to 175%, or about 20% to 150% compared to the subject administered either Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, or venetoclax, or a pharmaceutically acceptable salt thereof. DB1 / 147901903.2 22 In yet another aspect, the present disclosure provides a method of determining whether a subject with a disease or disorder selected from an inflammatory disease or disorder, and a cancer selected from acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), can be treated by administration of Compound 8 or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, the method comprising: determining whether the subject has an elevated expression of one or more IRAK1 / 4-associated genes and / or a decreased expression of one or more IRAK1 / 4-associated genes, wherein the IRAK1 / 4-associated genes are selected from: PLS3, HSBP1L1, CDC42BPA, PPP2R3A, GNG12, PENK, STC2, DNAJC22, SH3D19, GABRD, RAVER2, ARHGEF26, APBB2, BAI2, DPEP1, LGI2, PIP5K1A, SOX18, BMP4, TMC4, KCNIP3, CCNO, ULK4P2, FAM57A, SCARA3, CERS1, BEND5, HAPLN3, DNMBP, KIAA1522, PIR, GTF3C5 ECHDC3, ICAM1, RAB3A, SDHA, C9orf116, MKI67, LMTK3, MCM10, ADM2, HSD17B14, LOC102724002, KCNH2, PRAME, KIAA1279, LOC101929974, ARHGAP21, SULT2B1, ADCY6, GBF1, TUBGCP2, CD19, SPIRE2, SH3PXD2B, AADAT, FOXC1, ZBED3, TSKU, NRARP, AMIGO2, PCBD1, TCAM1P, FAM57B, LOC101929021, PCK2, CCDC127, MGMT, C6orf147, TGFB1I1, DPP4, ALX4, TACC2, WLS, PACSIN3, NAPA-AS1, LINC00999, BAIAP3, ANKH, VDAC2, TAF3, ECHS1, EFNA3, CORO6, TCTN2, HPS1, DNAJB12, SPIB, SLC29A3, PHGDH, PTMS, TMEM91, SEC24C, HGD, MSS51, TEAD3, LARP4B, ZCCHC24, ARHGEF16, FOXO6, FBXO18, PPRC1, CCDC78, RHBDL1, SPINT1, STON2, NUDT8, NEBL, EPAS1, FAM178A, PI4K2A, SNED1, STAM, PLOD2, TM7SF2, FGD1, PCDHB6, CCNB3, MCMDC2, EDRF1, NRM, PPIF, ATF5, BRD9, B3GALT4, NET1, TMEM169, RPH3AL, DROSHA, RBMS2, POLR3A, TRIP13, LPHN1, ZMIZ1, RP11-344B5.2, HNRNPF, HSD17B7P2, SLIT1, LOC648987, ACTR1A, CCT5, S1PR5, WDFY4, GRK5, SREBF1, STXBP5L, VARS2, GAB2, ZFP36L1, CPNE7, HSPA2, NAT8L, DOK4, IGF1R, KHK, KIRREL2, COMTD1, ZNF488, CASC10, QRICH2, RBM17, LSS, PAX8, PKN3, HELLS, FN3K, CDC42EP1, NFIX, BMS1, STOX1, SEMA4B, SUPV3L1, FAM198A, RCOR2, PDCD4, PPAP2A, DDX12P, ACY3, TSPAN10, NUP155, RIBC2, PLCXD1, TP53INP2, GOLPH3, WDR70, BTRC, SVIL, DTX4, DUSP5, ECE1, MRPL43, SKP2, SNHG3, MYRF, ZFYVE27, H2AFY2, NOLC1, SLC25A28, WNK2, NDUFS6, SLC30A3, LOC642846, NEURL1B, ARMC4, SFXN3, VASH2, NOTUM, VCL, LOC100506901, CSTF2T, PRICKLE1, ZNF132, GPR153, ZMYND11, DGCR5, OXER1, VTI1A, PCDHGC3, MORC4, EIF3A, PDCD11, SLC38A1, MC1R, CBS, AC002454.1, DB1 / 147901903.2 23 PDCD6, B4GALNT1, RPP38, SUGT1P1, NEDD4L, PROCA1, SH3PXD2A, JAG2, FGFR3, TMEM191B, SEPHS1, LOC100505761, C21orf58, FADS1, TET1, GBGT1, KAT6B, KIFC2, TAF5, CASP7, PELI3, PP7080, ATN1, KIAA1598, FAM115A, NKX3-2, CHCHD10, GPSM1, LRP4, CDT1, EIF4EBP2, AASS, ABCC6P1, ABCD2, ADAMTS14, AGAP4, AGAP9, AIFM2, AKR1C1, AKR1E2, ANK3, ANKRD33B, ANO6, APBB1IP, ARHGAP19, ARNTL2, ARSG, ARTN, ASCC1, ASUN, BAG3, BEND4, BEX5, BLNK, BTAF1, C10orf10, C10orf12, C10orf76, C10orf91, C15orf38, C2CD4C, C2CD5, C3orf18, CALHM2, CAMK1D, CAPRIN2, CDH2, CDHR1, CEL, CEP72, CES3, CES4A, CHST3, CLIC5, CMAS, CNNM2, CNTN1, COL27A1, COL4A5, CPS1, CRABP1, CTBP2, CUEDC2, CXorf57, DAPK2, DDAH2, DDX11, DDX11-AS1, DENND5B, DHTKD1, DNM1L, DPCD, DPY19L2, DUSP5P1, EBF3, EFEMP2, EGFR, ELK1, EPHB4, FAM155B, FAM175B, FAM21C, FAM45A, FAM53B, FAM84B, FCER2, FGD4, FOXL2, FZD8, GAS1, GPC6, GRIA3, GUCY1B3, GYPE, HDHD3, HES4, HIF1AN, HMGCS1, HMX2, HMX3, HOXB13, HOXB6, HSD17B8, HSH2D, IDE, INPP5A, INPP5F, INPP5J, IPO8, IRAK4, ITPR2, ITPR3, JMJD1C, KAZALD1, KCNQ5, KCNS3, KIAA1324, KIF11, KLHL42, KLLN, KRAS, KREMEN2, LAT, LDB1, LGALS3BP, LINC00477, LIPE, LOC100288152, LOC100506688, LOC100506691, LOC100507487, LOC101927104, LOC101927799, LOC101928913, LOC102723337, LOC102724472, LPCAT1, LRMP, LRRC10B, LRRC20, LRRC27, LTK, LY6G5C, LZTS2, MAP2K6, MASTL, MCIDAS, MCMBP, MDGA2, METTL12, METTL20, MMS19, MPPED2, MRPS16, MRPS35, MSX1, MX1, NDUFB8, NEURL1, NEUROG3, NFKB2, NIM1K, NKD2, NLGN2, NNT, NNT-AS1, NT5DC2, NUDT13, OGDHL, OVOL2, OXCT1, P2RX7, P4HA1, PABPC1L, PANK1, PAOX, PAPD7, PAPSS2, PCDHB13, PCDHB14, PCED1B, PCED1B-AS1, PCSK5, PDLIM1, PEAR1, PFKP, PGAM1, PGAM4, PI15, PITX1, PLEKHA8P1, PLEKHO1, PPFIBP1, PPP2R2D, PPP3CB, PRTFDC1, PSTPIP2, PTENP1, PVRL3, PWWP2B, PXDC1, RNF208, ROBO1, RP11-184I16.4, RP11-53O19.1, RP11-96H19.1, RPAP3, RTN1, SAMD11, SAMD8, SCAF11, SCD5, SDHAP3, SEC14L2, SEC31B, SEC61A2, SECTM1, SFMBT2, SFXN2, SHANK3, SHISA3, SHISA7, SIDT1, SKIDA1, SLA2, SLC12A7, SLC16A6, SLC16A9, SLC4A11, SLITRK5, SMAD1, SNHG12, SNORA61, SNORD104, SOX1, SPEF2, SRRM3, SUFU, TARS, TCF7, TEX15, TGFBR3L, THBD, TIAL1, TLX3, TM7SF3, TMEM180, TMEM191C, TMEM255A, TMEM63C, TRIM72, TUBB3, TYSND1, UGT3A2, ULK2, UNC13D, USP54, VENTX, VIM, XPNPEP1, YARS2, YPEL3, ZDHHC16, ZDHHC6, ZNF43, ZNF438, ZNF503, DB1 / 147901903.2 24 ZNF503-AS2, ZNF511, ZNF574, ZNF622, ZNF726, ZNF99, ZWINT, ADM, ALDOC, BNIP3, CA3, CD209, CSMD3, DDIT4, FCGR2B, FCGR2C, FIGN, GLIS2, SHISA8, SOX5, TBC1D30, TLE6, TLX1, VAT1L, VEGFA, ANXA4, APLN, C1QL4, CCDC102A, CHDH, EGLN3, ENO2, FADS2, HK2, HSPA7, IL17RB, KLF2, LAMC, LINC00263, LOC101928092, LOC102724908, MIR210HG, NRTN, PFKFB4, SCD, SLC4A3, SLC6A8, ZNF215, and ZNF395; optionally wherein the IRAK1 / 4-associated genes are selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3. In one embodiment, the subject has elevated expression of one or more IRAK1 / 4-associated genes compared to a healthy control subject and / or a decreased expression of one or more IRAK1 / 4-associated genes compared to a healthy control subject. In one embodiment, the subject in need thereof has an elevated expression of one or more IRAK1 / 4-associated genes selected from: PLS3, HSBP1L1, CDC42BPA, PPP2R3A, GNG12, PENK, STC2, DNAJC22, SH3D19, GABRD, RAVER2, ARHGEF26, APBB2, BAI2, DPEP1, LGI2, PIP5K1A, SOX18, BMP4, TMC4, KCNIP3, CCNO, ULK4P2, FAM57A, SCARA3, CERS1, BEND5, HAPLN3, DNMBP, KIAA1522, PIR, GTF3C5 ECHDC3, ICAM1, RAB3A, SDHA, C9orf116, MKI67, LMTK3, MCM10, ADM2, HSD17B14, LOC102724002, KCNH2, PRAME, KIAA1279, LOC101929974, ARHGAP21, SULT2B1, ADCY6, GBF1, TUBGCP2, CD19, SPIRE2, SH3PXD2B, AADAT, FOXC1, ZBED3, TSKU, NRARP, AMIGO2, PCBD1, TCAM1P, FAM57B, LOC101929021, PCK2, CCDC127, MGMT, C6orf147, TGFB1I1, DPP4, ALX4, TACC2, WLS, PACSIN3, NAPA-AS1, LINC00999, BAIAP3, ANKH, VDAC2, TAF3, ECHS1, EFNA3, CORO6, TCTN2, HPS1, DNAJB12, SPIB, SLC29A3, PHGDH, PTMS, TMEM91, SEC24C, HGD, MSS51, TEAD3, LARP4B, ZCCHC24, ARHGEF16, FOXO6, FBXO18, PPRC1, CCDC78, RHBDL1, SPINT1, STON2, NUDT8, NEBL, EPAS1, FAM178A, PI4K2A, SNED1, STAM, PLOD2, TM7SF2, FGD1, PCDHB6, CCNB3, MCMDC2, EDRF1, NRM, PPIF, ATF5, BRD9, B3GALT4, NET1, TMEM169, RPH3AL, DROSHA, RBMS2, POLR3A, TRIP13, LPHN1, ZMIZ1, RP11-344B5.2, HNRNPF, HSD17B7P2, SLIT1, LOC648987, ACTR1A, CCT5, S1PR5, WDFY4, GRK5, SREBF1, STXBP5L, VARS2, GAB2, DB1 / 147901903.2 25 ZFP36L1, CPNE7, HSPA2, NAT8L, DOK4, IGF1R, KHK, KIRREL2, COMTD1, ZNF488, CASC10, QRICH2, RBM17, LSS, PAX8, PKN3, HELLS, FN3K, CDC42EP1, NFIX, BMS1, STOX1, SEMA4B, SUPV3L1, FAM198A, RCOR2, PDCD4, PPAP2A, DDX12P, ACY3, TSPAN10, NUP155, RIBC2, PLCXD1, TP53INP2, GOLPH3, WDR70, BTRC, SVIL, DTX4, DUSP5, ECE1, MRPL43, SKP2, SNHG3, MYRF, ZFYVE27, H2AFY2, NOLC1, SLC25A28, WNK2, NDUFS6, SLC30A3, LOC642846, NEURL1B, ARMC4, SFXN3, VASH2, NOTUM, VCL, LOC100506901, CSTF2T, PRICKLE1, ZNF132, GPR153, ZMYND11, DGCR5, OXER1, VTI1A, PCDHGC3, MORC4, EIF3A, PDCD11, SLC38A1, MC1R, CBS, AC002454.1, PDCD6, B4GALNT1, RPP38, SUGT1P1, NEDD4L, PROCA1, SH3PXD2A, JAG2, FGFR3, TMEM191B, SEPHS1, LOC100505761, C21orf58, FADS1, TET1, GBGT1, KAT6B, KIFC2, TAF5, CASP7, PELI3, PP7080, ATN1, KIAA1598, FAM115A, NKX3-2, CHCHD10, GPSM1, LRP4, CDT1, EIF4EBP2, AASS, ABCC6P1, ABCD2, ADAMTS14, AGAP4, AGAP9, AIFM2, AKR1C1, AKR1E2, ANK3, ANKRD33B, ANO6, APBB1IP, ARHGAP19, ARNTL2, ARSG, ARTN, ASCC1, ASUN, BAG3, BEND4, BEX5, BLNK, BTAF1, C10orf10, C10orf12, C10orf76, C10orf91, C15orf38, C2CD4C, C2CD5, C3orf18, CALHM2, CAMK1D, CAPRIN2, CDH2, CDHR1, CEL, CEP72, CES3, CES4A, CHST3, CLIC5, CMAS, CNNM2, CNTN1, COL27A1, COL4A5, CPS1, CRABP1, CTBP2, CUEDC2, CXorf57, DAPK2, DDAH2, DDX11, DDX11-AS1, DENND5B, DHTKD1, DNM1L, DPCD, DPY19L2, DUSP5P1, EBF3, EFEMP2, EGFR, ELK1, EPHB4, FAM155B, FAM175B, FAM21C, FAM45A, FAM53B, FAM84B, FCER2, FGD4, FOXL2, FZD8, GAS1, GPC6, GRIA3, GUCY1B3, GYPE, HDHD3, HES4, HIF1AN, HMGCS1, HMX2, HMX3, HOXB13, HOXB6, HSD17B8, HSH2D, IDE, INPP5A, INPP5F, INPP5J, IPO8, IRAK4, ITPR2, ITPR3, JMJD1C, KAZALD1, KCNQ5, KCNS3, KIAA1324, KIF11, KLHL42, KLLN, KRAS, KREMEN2, LAT, LDB1, LGALS3BP, LINC00477, LIPE, LOC100288152, LOC100506688, LOC100506691, LOC100507487, LOC101927104, LOC101927799, LOC101928913, LOC102723337, LOC102724472, LPCAT1, LRMP, LRRC10B, LRRC20, LRRC27, LTK, LY6G5C, LZTS2, MAP2K6, MASTL, MCIDAS, MCMBP, MDGA2, METTL12, METTL20, MMS19, MPPED2, MRPS16, MRPS35, MSX1, MX1, NDUFB8, NEURL1, NEUROG3, NFKB2, NIM1K, NKD2, NLGN2, NNT, NNT-AS1, NT5DC2, NUDT13, OGDHL, OVOL2, OXCT1, P2RX7, P4HA1, PABPC1L, PANK1, PAOX, PAPD7, PAPSS2, PCDHB13, PCDHB14, PCED1B, PCED1B-AS1, PCSK5, PDLIM1, PEAR1, PFKP, PGAM1, PGAM4, PI15, PITX1, PLEKHA8P1, PLEKHO1, PPFIBP1, PPP2R2D, DB1 / 147901903.2 26 PPP3CB, PRTFDC1, PSTPIP2, PTENP1, PVRL3, PWWP2B, PXDC1, RNF208, ROBO1, RP11-184I16.4, RP11-53O19.1, RP11-96H19.1, RPAP3, RTN1, SAMD11, SAMD8, SCAF11, SCD5, SDHAP3, SEC14L2, SEC31B, SEC61A2, SECTM1, SFMBT2, SFXN2, SHANK3, SHISA3, SHISA7, SIDT1, SKIDA1, SLA2, SLC12A7, SLC16A6, SLC16A9, SLC4A11, SLITRK5, SMAD1, SNHG12, SNORA61, SNORD104, SOX1, SPEF2, SRRM3, SUFU, TARS, TCF7, TEX15, TGFBR3L, THBD, TIAL1, TLX3, TM7SF3, TMEM180, TMEM191C, TMEM255A, TMEM63C, TRIM72, TUBB3, TYSND1, UGT3A2, ULK2, UNC13D, USP54, VENTX, VIM, XPNPEP1, YARS2, YPEL3, ZDHHC16, ZDHHC6, ZNF43, ZNF438, ZNF503, ZNF503-AS2, ZNF511, ZNF574, ZNF622, ZNF726, ZNF99, ZWINT, ADM, ALDOC, BNIP3, CA3, CD209, CSMD3, DDIT4, FCGR2B, FCGR2C, FIGN, GLIS2, SHISA8, SOX5, TBC1D30, TLE6, TLX1, VAT1L, VEGFA, ANXA4, APLN, C1QL4, CCDC102A, CHDH, EGLN3, ENO2, FADS2, HK2, HSPA7, IL17RB, KLF2, LAMC, LINC00263, LOC101928092, LOC102724908, MIR210HG, NRTN, PFKFB4, SCD, SLC4A3, SLC6A8, ZNF215, and ZNF395; optionally wherein the subject in need thereof has elevated expression of one or more IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3. In one embodiment, the subject in need thereof has a decreased expression of one or more IRAK1 / 4- associated genes selected from: PLS3, HSBP1L1, CDC42BPA, PPP2R3A, GNG12, PENK, STC2, DNAJC22, SH3D19, GABRD, RAVER2, ARHGEF26, APBB2, BAI2, DPEP1, LGI2, PIP5K1A, SOX18, BMP4, TMC4, KCNIP3, CCNO, ULK4P2, FAM57A, SCARA3, CERS1, BEND5, HAPLN3, DNMBP, KIAA1522, PIR, GTF3C5 ECHDC3, ICAM1, RAB3A, SDHA, C9orf116, MKI67, LMTK3, MCM10, ADM2, HSD17B14, LOC102724002, KCNH2, PRAME, KIAA1279, LOC101929974, ARHGAP21, SULT2B1, ADCY6, GBF1, TUBGCP2, CD19, SPIRE2, SH3PXD2B, AADAT, FOXC1, ZBED3, TSKU, NRARP, AMIGO2, PCBD1, TCAM1P, FAM57B, LOC101929021, PCK2, CCDC127, MGMT, C6orf147, TGFB1I1, DPP4, ALX4, TACC2, WLS, PACSIN3, NAPA-AS1, LINC00999, BAIAP3, ANKH, VDAC2, TAF3, ECHS1, EFNA3, CORO6, TCTN2, HPS1, DNAJB12, SPIB, SLC29A3, PHGDH, PTMS, DB1 / 147901903.2 27 TMEM91, SEC24C, HGD, MSS51, TEAD3, LARP4B, ZCCHC24, ARHGEF16, FOXO6, FBXO18, PPRC1, CCDC78, RHBDL1, SPINT1, STON2, NUDT8, NEBL, EPAS1, FAM178A, PI4K2A, SNED1, STAM, PLOD2, TM7SF2, FGD1, PCDHB6, CCNB3, MCMDC2, EDRF1, NRM, PPIF, ATF5, BRD9, B3GALT4, NET1, TMEM169, RPH3AL, DROSHA, RBMS2, POLR3A, TRIP13, LPHN1, ZMIZ1, RP11-344B5.2, HNRNPF, HSD17B7P2, SLIT1, LOC648987, ACTR1A, CCT5, S1PR5, WDFY4, GRK5, SREBF1, STXBP5L, VARS2, GAB2, ZFP36L1, CPNE7, HSPA2, NAT8L, DOK4, IGF1R, KHK, KIRREL2, COMTD1, ZNF488, CASC10, QRICH2, RBM17, LSS, PAX8, PKN3, HELLS, FN3K, CDC42EP1, NFIX, BMS1, STOX1, SEMA4B, SUPV3L1, FAM198A, RCOR2, PDCD4, PPAP2A, DDX12P, ACY3, TSPAN10, NUP155, RIBC2, PLCXD1, TP53INP2, GOLPH3, WDR70, BTRC, SVIL, DTX4, DUSP5, ECE1, MRPL43, SKP2, SNHG3, MYRF, ZFYVE27, H2AFY2, NOLC1, SLC25A28, WNK2, NDUFS6, SLC30A3, LOC642846, NEURL1B, ARMC4, SFXN3, VASH2, NOTUM, VCL, LOC100506901, CSTF2T, PRICKLE1, ZNF132, GPR153, ZMYND11, DGCR5, OXER1, VTI1A, PCDHGC3, MORC4, EIF3A, PDCD11, SLC38A1, MC1R, CBS, AC002454.1, PDCD6, B4GALNT1, RPP38, SUGT1P1, NEDD4L, PROCA1, SH3PXD2A, JAG2, FGFR3, TMEM191B, SEPHS1, LOC100505761, C21orf58, FADS1, TET1, GBGT1, KAT6B, KIFC2, TAF5, CASP7, PELI3, PP7080, ATN1, KIAA1598, FAM115A, NKX3-2, CHCHD10, GPSM1, LRP4, CDT1, EIF4EBP2, AASS, ABCC6P1, ABCD2, ADAMTS14, AGAP4, AGAP9, AIFM2, AKR1C1, AKR1E2, ANK3, ANKRD33B, ANO6, APBB1IP, ARHGAP19, ARNTL2, ARSG, ARTN, ASCC1, ASUN, BAG3, BEND4, BEX5, BLNK, BTAF1, C10orf10, C10orf12, C10orf76, C10orf91, C15orf38, C2CD4C, C2CD5, C3orf18, CALHM2, CAMK1D, CAPRIN2, CDH2, CDHR1, CEL, CEP72, CES3, CES4A, CHST3, CLIC5, CMAS, CNNM2, CNTN1, COL27A1, COL4A5, CPS1, CRABP1, CTBP2, CUEDC2, CXorf57, DAPK2, DDAH2, DDX11, DDX11-AS1, DENND5B, DHTKD1, DNM1L, DPCD, DPY19L2, DUSP5P1, EBF3, EFEMP2, EGFR, ELK1, EPHB4, FAM155B, FAM175B, FAM21C, FAM45A, FAM53B, FAM84B, FCER2, FGD4, FOXL2, FZD8, GAS1, GPC6, GRIA3, GUCY1B3, GYPE, HDHD3, HES4, HIF1AN, HMGCS1, HMX2, HMX3, HOXB13, HOXB6, HSD17B8, HSH2D, IDE, INPP5A, INPP5F, INPP5J, IPO8, IRAK4, ITPR2, ITPR3, JMJD1C, KAZALD1, KCNQ5, KCNS3, KIAA1324, KIF11, KLHL42, KLLN, KRAS, KREMEN2, LAT, LDB1, LGALS3BP, LINC00477, LIPE, LOC100288152, LOC100506688, LOC100506691, LOC100507487, LOC101927104, LOC101927799, LOC101928913, LOC102723337, LOC102724472, LPCAT1, DB1 / 147901903.2 28 LRMP, LRRC10B, LRRC20, LRRC27, LTK, LY6G5C, LZTS2, MAP2K6, MASTL, MCIDAS, MCMBP, MDGA2, METTL12, METTL20, MMS19, MPPED2, MRPS16, MRPS35, MSX1, MX1, NDUFB8, NEURL1, NEUROG3, NFKB2, NIM1K, NKD2, NLGN2, NNT, NNT-AS1, NT5DC2, NUDT13, OGDHL, OVOL2, OXCT1, P2RX7, P4HA1, PABPC1L, PANK1, PAOX, PAPD7, PAPSS2, PCDHB13, PCDHB14, PCED1B, PCED1B-AS1, PCSK5, PDLIM1, PEAR1, PFKP, PGAM1, PGAM4, PI15, PITX1, PLEKHA8P1, PLEKHO1, PPFIBP1, PPP2R2D, PPP3CB, PRTFDC1, PSTPIP2, PTENP1, PVRL3, PWWP2B, PXDC1, RNF208, ROBO1, RP11-184I16.4, RP11-53O19.1, RP11-96H19.1, RPAP3, RTN1, SAMD11, SAMD8, SCAF11, SCD5, SDHAP3, SEC14L2, SEC31B, SEC61A2, SECTM1, SFMBT2, SFXN2, SHANK3, SHISA3, SHISA7, SIDT1, SKIDA1, SLA2, SLC12A7, SLC16A6, SLC16A9, SLC4A11, SLITRK5, SMAD1, SNHG12, SNORA61, SNORD104, SOX1, SPEF2, SRRM3, SUFU, TARS, TCF7, TEX15, TGFBR3L, THBD, TIAL1, TLX3, TM7SF3, TMEM180, TMEM191C, TMEM255A, TMEM63C, TRIM72, TUBB3, TYSND1, UGT3A2, ULK2, UNC13D, USP54, VENTX, VIM, XPNPEP1, YARS2, YPEL3, ZDHHC16, ZDHHC6, ZNF43, ZNF438, ZNF503, ZNF503-AS2, ZNF511, ZNF574, ZNF622, ZNF726, ZNF99, ZWINT, ADM, ALDOC, BNIP3, CA3, CD209, CSMD3, DDIT4, FCGR2B, FCGR2C, FIGN, GLIS2, SHISA8, SOX5, TBC1D30, TLE6, TLX1, VAT1L, VEGFA, ANXA4, APLN, C1QL4, CCDC102A, CHDH, EGLN3, ENO2, FADS2, HK2, HSPA7, IL17RB, KLF2, LAMC, LINC00263, LOC101928092, LOC102724908, MIR210HG, NRTN, PFKFB4, SCD, SLC4A3, SLC6A8, ZNF215, and ZNF395, optionally wherein the subject in need thereof has decreased expression of one or more IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3. In one embodiment, Compound 8 decreases the expression of one or more IRAK1 / 4-associated genes found to be elevated in the subject, and / or increases the expression of one or more IRAK1 / 4- associated genes found to be decreased in the subject. In one embodiment, Compound 8 decreases the expression of the one or more IRAK1 / 4-associated genes found to be elevated in the subject before the administration of Compound 8, and / or increases the expression of the one DB1 / 147901903.2 29 or more IRAK1 / 4-associated genes found to be decreased in the subject before the administration of Compound 8. In one embodiment, Compound 8 decreases the expression of one or more IRAK1 / 4-associated genes found to be elevated in the subject compared to a healthy control subject, and / or increases the expression of one or more IRAK1 / 4-associated genes found to be decreased in the subject compared to a healthy control subject. In one embodiment, Compound 8 decreases the expression of one or more IRAK1 / 4-associated genes selected from: PLS3, HSBP1L1, CDC42BPA, PPP2R3A, GNG12, PENK, STC2, DNAJC22, SH3D19, GABRD, RAVER2, ARHGEF26, APBB2, BAI2, DPEP1, LGI2, PIP5K1A, SOX18, BMP4, TMC4, KCNIP3, CCNO, ULK4P2, FAM57A, SCARA3, CERS1, BEND5, HAPLN3, DNMBP, KIAA1522, PIR, GTF3C5 ECHDC3, ICAM1, RAB3A, SDHA, C9orf116, MKI67, LMTK3, MCM10, ADM2, HSD17B14, LOC102724002, KCNH2, PRAME, KIAA1279, LOC101929974, ARHGAP21, SULT2B1, ADCY6, GBF1, TUBGCP2, CD19, SPIRE2, SH3PXD2B, AADAT, FOXC1, ZBED3, TSKU, NRARP, AMIGO2, PCBD1, TCAM1P, FAM57B, LOC101929021, PCK2, CCDC127, MGMT, C6orf147, TGFB1I1, DPP4, ALX4, TACC2, WLS, PACSIN3, NAPA-AS1, LINC00999, BAIAP3, ANKH, VDAC2, TAF3, ECHS1, EFNA3, CORO6, TCTN2, HPS1, DNAJB12, SPIB, SLC29A3, PHGDH, PTMS, TMEM91, SEC24C, HGD, MSS51, TEAD3, LARP4B, ZCCHC24, ARHGEF16, FOXO6, FBXO18, PPRC1, CCDC78, RHBDL1, SPINT1, STON2, NUDT8, NEBL, EPAS1, FAM178A, PI4K2A, SNED1, STAM, PLOD2, TM7SF2, FGD1, PCDHB6, CCNB3, MCMDC2, EDRF1, NRM, PPIF, ATF5, BRD9, B3GALT4, NET1, TMEM169, RPH3AL, DROSHA, RBMS2, POLR3A, TRIP13, LPHN1, ZMIZ1, RP11-344B5.2, HNRNPF, HSD17B7P2, SLIT1, LOC648987, ACTR1A, CCT5, S1PR5, WDFY4, GRK5, SREBF1, STXBP5L, VARS2, GAB2, ZFP36L1, CPNE7, HSPA2, NAT8L, DOK4, IGF1R, KHK, KIRREL2, COMTD1, ZNF488, CASC10, QRICH2, RBM17, LSS, PAX8, PKN3, HELLS, FN3K, CDC42EP1, NFIX, BMS1, STOX1, SEMA4B, SUPV3L1, FAM198A, RCOR2, PDCD4, PPAP2A, DDX12P, ACY3, TSPAN10, NUP155, RIBC2, PLCXD1, TP53INP2, GOLPH3, WDR70, BTRC, SVIL, DTX4, DUSP5, ECE1, MRPL43, SKP2, SNHG3, MYRF, ZFYVE27, H2AFY2, NOLC1, SLC25A28, WNK2, NDUFS6, SLC30A3, LOC642846, NEURL1B, ARMC4, SFXN3, VASH2, NOTUM, VCL, LOC100506901, CSTF2T, PRICKLE1, ZNF132, GPR153, ZMYND11, DGCR5, OXER1, VTI1A, PCDHGC3, MORC4, EIF3A, PDCD11, SLC38A1, MC1R, CBS, AC002454.1, PDCD6, B4GALNT1, RPP38, SUGT1P1, NEDD4L, PROCA1, SH3PXD2A, JAG2, FGFR3, DB1 / 147901903.2 30 TMEM191B, SEPHS1, LOC100505761, C21orf58, FADS1, TET1, GBGT1, KAT6B, KIFC2, TAF5, CASP7, PELI3, PP7080, ATN1, KIAA1598, FAM115A, NKX3-2, CHCHD10, GPSM1, LRP4, CDT1, EIF4EBP2, AASS, ABCC6P1, ABCD2, ADAMTS14, AGAP4, AGAP9, AIFM2, AKR1C1, AKR1E2, ANK3, ANKRD33B, ANO6, APBB1IP, ARHGAP19, ARNTL2, ARSG, ARTN, ASCC1, ASUN, BAG3, BEND4, BEX5, BLNK, BTAF1, C10orf10, C10orf12, C10orf76, C10orf91, C15orf38, C2CD4C, C2CD5, C3orf18, CALHM2, CAMK1D, CAPRIN2, CDH2, CDHR1, CEL, CEP72, CES3, CES4A, CHST3, CLIC5, CMAS, CNNM2, CNTN1, COL27A1, COL4A5, CPS1, CRABP1, CTBP2, CUEDC2, CXorf57, DAPK2, DDAH2, DDX11, DDX11-AS1, DENND5B, DHTKD1, DNM1L, DPCD, DPY19L2, DUSP5P1, EBF3, EFEMP2, EGFR, ELK1, EPHB4, FAM155B, FAM175B, FAM21C, FAM45A, FAM53B, FAM84B, FCER2, FGD4, FOXL2, FZD8, GAS1, GPC6, GRIA3, GUCY1B3, GYPE, HDHD3, HES4, HIF1AN, HMGCS1, HMX2, HMX3, HOXB13, HOXB6, HSD17B8, HSH2D, IDE, INPP5A, INPP5F, INPP5J, IPO8, IRAK4, ITPR2, ITPR3, JMJD1C, KAZALD1, KCNQ5, KCNS3, KIAA1324, KIF11, KLHL42, KLLN, KRAS, KREMEN2, LAT, LDB1, LGALS3BP, LINC00477, LIPE, LOC100288152, LOC100506688, LOC100506691, LOC100507487, LOC101927104, LOC101927799, LOC101928913, LOC102723337, LOC102724472, LPCAT1, LRMP, LRRC10B, LRRC20, LRRC27, LTK, LY6G5C, LZTS2, MAP2K6, MASTL, MCIDAS, MCMBP, MDGA2, METTL12, METTL20, MMS19, MPPED2, MRPS16, MRPS35, MSX1, MX1, NDUFB8, NEURL1, NEUROG3, NFKB2, NIM1K, NKD2, NLGN2, NNT, NNT-AS1, NT5DC2, NUDT13, OGDHL, OVOL2, OXCT1, P2RX7, P4HA1, PABPC1L, PANK1, PAOX, PAPD7, PAPSS2, PCDHB13, PCDHB14, PCED1B, PCED1B-AS1, PCSK5, PDLIM1, PEAR1, PFKP, PGAM1, PGAM4, PI15, PITX1, PLEKHA8P1, PLEKHO1, PPFIBP1, PPP2R2D, PPP3CB, PRTFDC1, PSTPIP2, PTENP1, PVRL3, PWWP2B, PXDC1, RNF208, ROBO1, RP11-184I16.4, RP11-53O19.1, RP11-96H19.1, RPAP3, RTN1, SAMD11, SAMD8, SCAF11, SCD5, SDHAP3, SEC14L2, SEC31B, SEC61A2, SECTM1, SFMBT2, SFXN2, SHANK3, SHISA3, SHISA7, SIDT1, SKIDA1, SLA2, SLC12A7, SLC16A6, SLC16A9, SLC4A11, SLITRK5, SMAD1, SNHG12, SNORA61, SNORD104, SOX1, SPEF2, SRRM3, SUFU, TARS, TCF7, TEX15, TGFBR3L, THBD, TIAL1, TLX3, TM7SF3, TMEM180, TMEM191C, TMEM255A, TMEM63C, TRIM72, TUBB3, TYSND1, UGT3A2, ULK2, UNC13D, USP54, VENTX, VIM, XPNPEP1, YARS2, YPEL3, ZDHHC16, ZDHHC6, ZNF43, ZNF438, ZNF503, ZNF503-AS2, ZNF511, ZNF574, ZNF622, ZNF726, ZNF99, ZWINT, ADM, ALDOC, BNIP3, DB1 / 147901903.2 31 CA3, CD209, CSMD3, DDIT4, FCGR2B, FCGR2C, FIGN, GLIS2, SHISA8, SOX5, TBC1D30, TLE6, TLX1, VAT1L, VEGFA, ANXA4, APLN, C1QL4, CCDC102A, CHDH, EGLN3, ENO2, FADS2, HK2, HSPA7, IL17RB, KLF2, LAMC, LINC00263, LOC101928092, LOC102724908, MIR210HG, NRTN, PFKFB4, SCD, SLC4A3, SLC6A8, ZNF215, and ZNF395 in the subject; optionally wherein the compound decreases the expression of one or more IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3 in the subject. In one embodiment, Compound 8 increases the expression of one or more IRAK1 / 4- associated genes selected from: PLS3, HSBP1L1, CDC42BPA, PPP2R3A, GNG12, PENK, STC2, DNAJC22, SH3D19, GABRD, RAVER2, ARHGEF26, APBB2, BAI2, DPEP1, LGI2, PIP5K1A, SOX18, BMP4, TMC4, KCNIP3, CCNO, ULK4P2, FAM57A, SCARA3, CERS1, BEND5, HAPLN3, DNMBP, KIAA1522, PIR, GTF3C5 ECHDC3, ICAM1, RAB3A, SDHA, C9orf116, MKI67, LMTK3, MCM10, ADM2, HSD17B14, LOC102724002, KCNH2, PRAME, KIAA1279, LOC101929974, ARHGAP21, SULT2B1, ADCY6, GBF1, TUBGCP2, CD19, SPIRE2, SH3PXD2B, AADAT, FOXC1, ZBED3, TSKU, NRARP, AMIGO2, PCBD1, TCAM1P, FAM57B, LOC101929021, PCK2, CCDC127, MGMT, C6orf147, TGFB1I1, DPP4, ALX4, TACC2, WLS, PACSIN3, NAPA-AS1, LINC00999, BAIAP3, ANKH, VDAC2, TAF3, ECHS1, EFNA3, CORO6, TCTN2, HPS1, DNAJB12, SPIB, SLC29A3, PHGDH, PTMS, TMEM91, SEC24C, HGD, MSS51, TEAD3, LARP4B, ZCCHC24, ARHGEF16, FOXO6, FBXO18, PPRC1, CCDC78, RHBDL1, SPINT1, STON2, NUDT8, NEBL, EPAS1, FAM178A, PI4K2A, SNED1, STAM, PLOD2, TM7SF2, FGD1, PCDHB6, CCNB3, MCMDC2, EDRF1, NRM, PPIF, ATF5, BRD9, B3GALT4, NET1, TMEM169, RPH3AL, DROSHA, RBMS2, POLR3A, TRIP13, LPHN1, ZMIZ1, RP11-344B5.2, HNRNPF, HSD17B7P2, SLIT1, LOC648987, ACTR1A, CCT5, S1PR5, WDFY4, GRK5, SREBF1, STXBP5L, VARS2, GAB2, ZFP36L1, CPNE7, HSPA2, NAT8L, DOK4, IGF1R, KHK, KIRREL2, COMTD1, ZNF488, CASC10, QRICH2, RBM17, LSS, PAX8, PKN3, HELLS, FN3K, CDC42EP1, NFIX, BMS1, STOX1, SEMA4B, SUPV3L1, FAM198A, RCOR2, PDCD4, PPAP2A, DDX12P, ACY3, DB1 / 147901903.2 32 TSPAN10, NUP155, RIBC2, PLCXD1, TP53INP2, GOLPH3, WDR70, BTRC, SVIL, DTX4, DUSP5, ECE1, MRPL43, SKP2, SNHG3, MYRF, ZFYVE27, H2AFY2, NOLC1, SLC25A28, WNK2, NDUFS6, SLC30A3, LOC642846, NEURL1B, ARMC4, SFXN3, VASH2, NOTUM, VCL, LOC100506901, CSTF2T, PRICKLE1, ZNF132, GPR153, ZMYND11, DGCR5, OXER1, VTI1A, PCDHGC3, MORC4, EIF3A, PDCD11, SLC38A1, MC1R, CBS, AC002454.1, PDCD6, B4GALNT1, RPP38, SUGT1P1, NEDD4L, PROCA1, SH3PXD2A, JAG2, FGFR3, TMEM191B, SEPHS1, LOC100505761, C21orf58, FADS1, TET1, GBGT1, KAT6B, KIFC2, TAF5, CASP7, PELI3, PP7080, ATN1, KIAA1598, FAM115A, NKX3-2, CHCHD10, GPSM1, LRP4, CDT1, EIF4EBP2, AASS, ABCC6P1, ABCD2, ADAMTS14, AGAP4, AGAP9, AIFM2, AKR1C1, AKR1E2, ANK3, ANKRD33B, ANO6, APBB1IP, ARHGAP19, ARNTL2, ARSG, ARTN, ASCC1, ASUN, BAG3, BEND4, BEX5, BLNK, BTAF1, C10orf10, C10orf12, C10orf76, C10orf91, C15orf38, C2CD4C, C2CD5, C3orf18, CALHM2, CAMK1D, CAPRIN2, CDH2, CDHR1, CEL, CEP72, CES3, CES4A, CHST3, CLIC5, CMAS, CNNM2, CNTN1, COL27A1, COL4A5, CPS1, CRABP1, CTBP2, CUEDC2, CXorf57, DAPK2, DDAH2, DDX11, DDX11-AS1, DENND5B, DHTKD1, DNM1L, DPCD, DPY19L2, DUSP5P1, EBF3, EFEMP2, EGFR, ELK1, EPHB4, FAM155B, FAM175B, FAM21C, FAM45A, FAM53B, FAM84B, FCER2, FGD4, FOXL2, FZD8, GAS1, GPC6, GRIA3, GUCY1B3, GYPE, HDHD3, HES4, HIF1AN, HMGCS1, HMX2, HMX3, HOXB13, HOXB6, HSD17B8, HSH2D, IDE, INPP5A, INPP5F, INPP5J, IPO8, IRAK4, ITPR2, ITPR3, JMJD1C, KAZALD1, KCNQ5, KCNS3, KIAA1324, KIF11, KLHL42, KLLN, KRAS, KREMEN2, LAT, LDB1, LGALS3BP, LINC00477, LIPE, LOC100288152, LOC100506688, LOC100506691, LOC100507487, LOC101927104, LOC101927799, LOC101928913, LOC102723337, LOC102724472, LPCAT1, LRMP, LRRC10B, LRRC20, LRRC27, LTK, LY6G5C, LZTS2, MAP2K6, MASTL, MCIDAS, MCMBP, MDGA2, METTL12, METTL20, MMS19, MPPED2, MRPS16, MRPS35, MSX1, MX1, NDUFB8, NEURL1, NEUROG3, NFKB2, NIM1K, NKD2, NLGN2, NNT, NNT-AS1, NT5DC2, NUDT13, OGDHL, OVOL2, OXCT1, P2RX7, P4HA1, PABPC1L, PANK1, PAOX, PAPD7, PAPSS2, PCDHB13, PCDHB14, PCED1B, PCED1B-AS1, PCSK5, PDLIM1, PEAR1, PFKP, PGAM1, PGAM4, PI15, PITX1, PLEKHA8P1, PLEKHO1, PPFIBP1, PPP2R2D, PPP3CB, PRTFDC1, PSTPIP2, PTENP1, PVRL3, PWWP2B, PXDC1, RNF208, ROBO1, RP11-184I16.4, RP11-53O19.1, RP11-96H19.1, RPAP3, RTN1, SAMD11, SAMD8, SCAF11, SCD5, SDHAP3, SEC14L2, SEC31B, SEC61A2, SECTM1, SFMBT2, SFXN2, SHANK3, DB1 / 147901903.2 33 SHISA3, SHISA7, SIDT1, SKIDA1, SLA2, SLC12A7, SLC16A6, SLC16A9, SLC4A11, SLITRK5, SMAD1, SNHG12, SNORA61, SNORD104, SOX1, SPEF2, SRRM3, SUFU, TARS, TCF7, TEX15, TGFBR3L, THBD, TIAL1, TLX3, TM7SF3, TMEM180, TMEM191C, TMEM255A, TMEM63C, TRIM72, TUBB3, TYSND1, UGT3A2, ULK2, UNC13D, USP54, VENTX, VIM, XPNPEP1, YARS2, YPEL3, ZDHHC16, ZDHHC6, ZNF43, ZNF438, ZNF503, ZNF503-AS2, ZNF511, ZNF574, ZNF622, ZNF726, ZNF99, ZWINT, ADM, ALDOC, BNIP3, CA3, CD209, CSMD3, DDIT4, FCGR2B, FCGR2C, FIGN, GLIS2, SHISA8, SOX5, TBC1D30, TLE6, TLX1, VAT1L, VEGFA, ANXA4, APLN, C1QL4, CCDC102A, CHDH, EGLN3, ENO2, FADS2, HK2, HSPA7, IL17RB, KLF2, LAMC, LINC00263, LOC101928092, LOC102724908, MIR210HG, NRTN, PFKFB4, SCD, SLC4A3, SLC6A8, ZNF215, and ZNF395 in the subject; optionally wherein the compound increases the expression of one or more IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3 in the subject. In yet another aspect, the present disclosure relates to a method of determining whether a subject with a disease or disorder selected from an inflammatory disease or disorder, and a cancer selected from acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), can be treated by the administration of Compound 8 or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, the method comprising: determining whether the subject has an elevated expression of one or more NFκB-associated genes, and / or a decreased expression of one or more NFκB-associated genes, wherein the NFκB-associated genes are selected from: A4, ABCA1, ABCB1, ABCB4, ABCB9, ABCC6, ABCG5, ABCG8, ADAM19, ADH1A, ADORA1, ADORA2A, ADRA2B. AFP, AGER, AGT, AHCTF1, AICDA, AKR1C1, ALOX12, ALOX5, AMACR, AMH, ANGPT1, APOBEC2, APOC3, APOD, APOE, AQP4, AR, ARFRP1, ART1, ASPH, ASS1, ATP1A2, B2M, BACE1, BAX, BCL2, BCL2A1, BCL2L1, BCL2L11, BCL3, BDKRB1, BDKRB1, BDNF, BGN, BLIMP1 / PRDM1, BLNK, BLR1, BMI1, BMP2, BMP4, BNIP3, BRCA2, BTK, C3, C4A, C4BPA, C69, CALCB, CASP4, CAV1, CCL1, DB1 / 147901903.2 34 CCL15, CCL17, CCL19, CCL2, CCL20, CCL22, CCL23, CCL28, CCL3, CCL4, CCL5, CCND1, CCND2, CCND3, CCR5, CCR7, CD209, CD274, CD38, CD3G, CD40, CD40LG, CD44, CD48, CD54, CD80, CD83, CD86, CDK6, CDKN1A, CDX1, CEBPD, CFB, CFLAR, CGM3, CHI3L1, CIDEA, CLDN2, COL1A2, CR2, CREB3, CRP, CSF1, CSF2, CSF3, CTSB, CTSL1, CXCL1, CXCL10, CXCL11, CXCL3, CXCL5, CXCL6, CXCL9, CYP19A1, CYP27B1, CYP2C11, CYP2E1, CYP7B1, DCTN4, DEFB2, DIO2, DMP1, DNASE1L2, DPYD, DUSP1, E2F3, EBI3, EDN1, EGFR, EGR1, ELF3, ENG, ENO2, EPHA1, EPO, ERBB2, ERVWE1, F11R, F3, F8, FABP6, FAM148A, FAS, FASLG, FCER2. FCER2 / CD23, FCGRT, FGF8, FN1, FOS, FSTL3, FTH1, G6PC, G6PD, GAD1, GADD45B, GATA3, GBP1, GCLC, GCLM, GCNT1, GJB1, GNAI2, GNB2L1, GNRH2, GRIN1, GRIN2A, GRM2, GRO-beta, GRO-gamma, GSTP1, GUCY1A2, GZMB, HAMP, HAS1, HBE1, HBZ, HGF, HIF1A, HLA-B, HLA-G, HMGN1, HMOX1, HOXA9, HPSE, HSD11B2, HSD17B8, HSP90AA1, ICOS, IDO1, IER2, IER3, IFI44L, IFNB, IFNG, IGFBP1, IGFBP2, IGHE, IGHG1, IGHG2, IGHG4, IGKC, Iigp1, IL10, IL11, IL12A, IL12B, IL13, IL15, IL17, IL1A, IL1B, IL1RN, IL2, IL23A, IL27, IL2RA, IL6, IL8, IL8RA, IL8RB, IL9, INHBA, IRF1, IRF2, IRF4, IRF7, JMJD3, JUNB, KC, KCNK5, KCNN2, KISS1, KITLG, KLF10, KLK3, KLRA1, KRT15, KRT3, KRT5, KRT6B, LAMB2, LBP, LCN2, LEF1, LGALS3, LIPG, LTA, LTB, LTF, LYZ, MADCAM1, MAP4K1, MBP, MDK, MMP1, MMP3, MMP9, MT3, MTHFR, MUC2, MX1, MYB, MYC, MYLK, MYOZ1, NCAM, NFKB1, NFKB2, NFKBIA, NFKBIE, NFKBIZ, NGFB, NK4, NLRP2, NOD2, NOS1, NOS2A, NOX1, NPY1R, NQO1, NR3C1, NR4A2, NRG1, NUAK2, OLR1, OPN1SW, OPRD1, OPRM1, ORM1, Osterix, OXTR, PAFAH2, PAX8, PDE7A, PDGFB, PDYN, PENK, PGK1, PGLYRP1, PGR, PI3KAP1, PIGF, pIgR, PIK3CA, PIM1, PLA2, PLAU, PLCD1, PLK3, POMC, PPARGC1B, PPP5C, PRF1, PRKACA, PRKCD, PRL, PSMB9, PSME1, PSME2, PTAFR,, PTEN, PTGDS, PTGES, PTGIS, PTGS2, PTHLH, PTPN1, PTPN13, PTS, PTX3, PYCARD, RAG1, RAG2, RBBP4, Rdh1, Rdh7, REL, RELB, REV3L, RIPK2, S100A10, S100A4, S100A6, SAA1, SAA2, SAA, SAT1, SCNN1A, SDC4, SELE, SELP, SELS, SENP2, SERPINA1, SERPINA2, SERPINA3, SERPINB1, SERPINE1, PAI-1, SERPINE2, SH3BGRL, SKALP, PI3, SKP2, SLC11A2, SLC16A1, SLC3A2, SLC6A6, Slfn2, SNAI1, SOD1, SOD2, SOX9, SPATA19, SPI1, SPP1, ST6GAL1, ST8SIA1, STAT5A, SUPV3L1, TACR1, TAP1, TAPBP, TCRB, TERT, TF, TFEC, TFF3, TFPI2, TGM1, TGM2, THBS1, THBS2, TICAM1, TIFA, TLR2, TLR9, TNC, TN, TNFAIP2, TNFAIP3, TNFRSF1B, DB1 / 147901903.2 35 TNFRSF4, TNFRSF9, TNFSF10, TNFSF13B, TNFSF13B, TNFSF15, TNIP1, TNIP3, TP53, TRAF1, TRAF2, TREM1, TRPC1, TWIST1, UBE2M, UCP2, UGCGL1, UPK1B, UPP1, VCAM1, VEGFC, VIM, VPS53, WNT10B, WT1, XDH, XIAP, YY1, and ZNF366. In one embodiment, the subject has elevated expression of one or more NFκB-associated genes compared to a healthy control subject and / or a decreased expression of one or more IRAK1 / 4- associated genes compared to a healthy control subject. In one embodiment, subject in need thereof has an elevated expression of one or more NFκB-associated genes selected from: A4, ABCA1, ABCB1, ABCB4, ABCB9, ABCC6, ABCG5, ABCG8, ADAM19, ADH1A, ADORA1, ADORA2A, ADRA2B. AFP, AGER, AGT, AHCTF1, AICDA, AKR1C1, ALOX12, ALOX5, AMACR, AMH, ANGPT1, APOBEC2, APOC3, APOD, APOE, AQP4, AR, ARFRP1, ART1, ASPH, ASS1, ATP1A2, B2M, BACE1, BAX, BCL2, BCL2A1, BCL2L1, BCL2L11, BCL3, BDKRB1, BDKRB1, BDNF, BGN, BLIMP1 / PRDM1, BLNK, BLR1, BMI1, BMP2, BMP4, BNIP3, BRCA2, BTK, C3, C4A, C4BPA, C69, CALCB, CASP4, CAV1, CCL1, CCL15, CCL17, CCL19, CCL2, CCL20, CCL22, CCL23, CCL28, CCL3, CCL4, CCL5, CCND1, CCND2, CCND3, CCR5, CCR7, CD209, CD274, CD38, CD3G, CD40, CD40LG, CD44, CD48, CD54, CD80, CD83, CD86, CDK6, CDKN1A, CDX1, CEBPD, CFB, CFLAR, CGM3, CHI3L1, CIDEA, CLDN2, COL1A2, CR2, CREB3, CRP, CSF1, CSF2, CSF3, CTSB, CTSL1, CXCL1, CXCL10, CXCL11, CXCL3, CXCL5, CXCL6, CXCL9, CYP19A1, CYP27B1, CYP2C11, CYP2E1, CYP7B1, DCTN4, DEFB2, DIO2, DMP1, DNASE1L2, DPYD, DUSP1, E2F3, EBI3, EDN1, EGFR, EGR1, ELF3, ENG, ENO2, EPHA1, EPO, ERBB2, ERVWE1, F11R, F3, F8, FABP6, FAM148A, FAS, FASLG, FCER2. FCER2 / CD23, FCGRT, FGF8, FN1, FOS, FSTL3, FTH1, G6PC, G6PD, GAD1, GADD45B, GATA3, GBP1, GCLC, GCLM, GCNT1, GJB1, GNAI2, GNB2L1, GNRH2, GRIN1, GRIN2A, GRM2, GRO-beta, GRO- gamma, GSTP1, GUCY1A2, GZMB, HAMP, HAS1, HBE1, HBZ, HGF, HIF1A, HLA-B, HLA-G, HMGN1, HMOX1, HOXA9, HPSE, HSD11B2, HSD17B8, HSP90AA1, ICOS, IDO1, IER2, IER3, IFI44L, IFNB, IFNG, IGFBP1, IGFBP2, IGHE, IGHG1, IGHG2, IGHG4, IGKC, Iigp1, IL10, IL11, IL12A, IL12B, IL13, IL15, IL17, IL1A, IL1B, IL1RN, IL2, IL23A, IL27, IL2RA, IL6, IL8, IL8RA, IL8RB, IL9, INHBA, IRF1, IRF2, IRF4, IRF7, JMJD3, JUNB, KC, KCNK5, KCNN2, KISS1, KITLG, KLF10, KLK3, KLRA1, KRT15, KRT3, KRT5, KRT6B, LAMB2, LBP, LCN2, LEF1, LGALS3, LIPG, LTA, LTB, LTF, LYZ, MADCAM1, MAP4K1, MBP, MDK, MMP1, MMP3, MMP9, MT3, MTHFR, MUC2, MX1, MYB, MYC, MYLK, DB1 / 147901903.2 36 MYOZ1, NCAM, NFKB1, NFKB2, NFKBIA, NFKBIE, NFKBIZ, NGFB, NK4, NLRP2, NOD2, NOS1, NOS2A, NOX1, NPY1R, NQO1, NR3C1, NR4A2, NRG1, NUAK2, OLR1, OPN1SW, OPRD1, OPRM1, ORM1, Osterix, OXTR, PAFAH2, PAX8, PDE7A, PDGFB, PDYN, PENK, PGK1, PGLYRP1, PGR, PI3KAP1, PIGF, pIgR, PIK3CA, PIM1, PLA2, PLAU, PLCD1, PLK3, POMC, PPARGC1B, PPP5C, PRF1, PRKACA, PRKCD, PRL, PSMB9, PSME1, PSME2, PTAFR, PTEN, PTGDS, PTGES, PTGIS, PTGS2, PTHLH, PTPN1, PTPN13, PTS, PTX3, PYCARD, RAG1, RAG2, RBBP4, Rdh1, Rdh7, REL, RELB, REV3L, RIPK2, S100A10, S100A4, S100A6, SAA1, SAA2, SAA, SAT1, SCNN1A, SDC4, SELE, SELP, SELS, SENP2, SERPINA1, SERPINA2, SERPINA3, SERPINB1, SERPINE1, PAI-1, SERPINE2, SH3BGRL, SKALP, PI3, SKP2, SLC11A2, SLC16A1, SLC3A2, SLC6A6, Slfn2, SNAI1, SOD1, SOD2, SOX9, SPATA19, SPI1, SPP1, ST6GAL1, ST8SIA1, STAT5A, SUPV3L1, TACR1, TAP1, TAPBP, TCRB, TERT, TF, TFEC, TFF3, TFPI2, TGM1, TGM2, THBS1, THBS2, TICAM1, TIFA, TLR2, TLR9, TNC, TN, TNFAIP2, TNFAIP3, TNFRSF1B, TNFRSF4, TNFRSF9, TNFSF10, TNFSF13B, TNFSF13B, TNFSF15, TNIP1, TNIP3, TP53, TRAF1, TRAF2, TREM1, TRPC1, TWIST1, UBE2M, UCP2, UGCGL1, UPK1B, UPP1, VCAM1, VEGFC, VIM, VPS53, WNT10B, WT1, XDH, XIAP, YY1, and ZNF366. In one embodiment, the subject in need thereof has a decreased expression of one or more NFκB- associated genes selected from: A4, ABCA1, ABCB1, ABCB4, ABCB9, ABCC6, ABCG5, ABCG8, ADAM19, ADH1A, ADORA1, ADORA2A, ADRA2B. AFP, AGER, AGT, AHCTF1, AICDA, AKR1C1, ALOX12, ALOX5, AMACR, AMH, ANGPT1, APOBEC2, APOC3, APOD, APOE, AQP4, AR, ARFRP1, ART1, ASPH, ASS1, ATP1A2, B2M, BACE1, BAX, BCL2, BCL2A1, BCL2L1, BCL2L11, BCL3, BDKRB1, BDKRB1, BDNF, BGN, BLIMP1 / PRDM1, BLNK, BLR1, BMI1, BMP2, BMP4, BNIP3, BRCA2, BTK, C3, C4A, C4BPA, C69, CALCB, CASP4, CAV1, CCL1, CCL15, CCL17, CCL19, CCL2, CCL20, CCL22, CCL23, CCL28, CCL3, CCL4, CCL5, CCND1, CCND2, CCND3, CCR5, CCR7, CD209, CD274, CD38, CD3G, CD40, CD40LG, CD44, CD48, CD54, CD80, CD83, CD86, CDK6, CDKN1A, CDX1, CEBPD, CFB, CFLAR, CGM3, CHI3L1, CIDEA, CLDN2, COL1A2, CR2, CREB3, CRP, CSF1, CSF2, CSF3, CTSB, CTSL1, CXCL1, CXCL10, CXCL11, CXCL3, CXCL5, CXCL6, CXCL9, CYP19A1, CYP27B1, CYP2C11, CYP2E1, CYP7B1, DCTN4, DEFB2, DIO2, DMP1, DNASE1L2, DPYD, DUSP1, E2F3, EBI3, EDN1, EGFR, EGR1, ELF3, ENG, ENO2, EPHA1, EPO, ERBB2, ERVWE1, F11R, F3, F8, FABP6, FAM148A, FAS, FASLG, FCER2. DB1 / 147901903.2 37 FCER2 / CD23, FCGRT, FGF8, FN1, FOS, FSTL3, FTH1, G6PC, G6PD, GAD1, GADD45B, GATA3, GBP1, GCLC, GCLM, GCNT1, GJB1, GNAI2, GNB2L1, GNRH2, GRIN1, GRIN2A, GRM2, GRO-beta, GRO-gamma, GSTP1, GUCY1A2, GZMB, HAMP, HAS1, HBE1, HBZ, HGF, HIF1A, HLA-B, HLA-G, HMGN1, HMOX1, HOXA9, HPSE, HSD11B2, HSD17B8, HSP90AA1, ICOS, IDO1, IER2, IER3, IFI44L, IFNB, IFNG, IGFBP1, IGFBP2, IGHE, IGHG1, IGHG2, IGHG4, IGKC, Iigp1, IL10, IL11, IL12A, IL12B, IL13, IL15, IL17, IL1A, IL1B, IL1RN, IL2, IL23A, IL27, IL2RA, IL6, IL8, IL8RA, IL8RB, IL9, INHBA, IRF1, IRF2, IRF4, IRF7, JMJD3, JUNB, KC, KCNK5, KCNN2, KISS1, KITLG, KLF10, KLK3, KLRA1, KRT15, KRT3, KRT5, KRT6B, LAMB2, LBP, LCN2, LEF1, LGALS3, LIPG, LTA, LTB, LTF, LYZ, MADCAM1, MAP4K1, MBP, MDK, MMP1, MMP3, MMP9, MT3, MTHFR, MUC2, MX1, MYB, MYC, MYLK, MYOZ1, NCAM, NFKB1, NFKB2, NFKBIA, NFKBIE, NFKBIZ, NGFB, NK4, NLRP2, NOD2, NOS1, NOS2A, NOX1, NPY1R, NQO1, NR3C1, NR4A2, NRG1, NUAK2, OLR1, OPN1SW, OPRD1, OPRM1, ORM1, Osterix, OXTR, PAFAH2, PAX8, PDE7A, PDGFB, PDYN, PENK, PGK1, PGLYRP1, PGR, PI3KAP1, PIGF, pIgR, PIK3CA, PIM1, PLA2, PLAU, PLCD1, PLK3, POMC, PPARGC1B, PPP5C, PRF1, PRKACA, PRKCD, PRL, PSMB9, PSME1, PSME2, PTAFR,, PTEN, PTGDS, PTGES, PTGIS, PTGS2, PTHLH, PTPN1, PTPN13, PTS, PTX3, PYCARD, RAG1, RAG2, RBBP4, Rdh1, Rdh7, REL, RELB, REV3L, RIPK2, S100A10, S100A4, S100A6, SAA1, SAA2, SAA, SAT1, SCNN1A, SDC4, SELE, SELP, SELS, SENP2, SERPINA1, SERPINA2, SERPINA3, SERPINB1, SERPINE1, PAI-1, SERPINE2, SH3BGRL, SKALP, PI3, SKP2, SLC11A2, SLC16A1, SLC3A2, SLC6A6, Slfn2, SNAI1, SOD1, SOD2, SOX9, SPATA19, SPI1, SPP1, ST6GAL1, ST8SIA1, STAT5A, SUPV3L1, TACR1, TAP1, TAPBP, TCRB, TERT, TF, TFEC, TFF3, TFPI2, TGM1, TGM2, THBS1, THBS2, TICAM1, TIFA, TLR2, TLR9, TNC, TN, TNFAIP2, TNFAIP3, TNFRSF1B, TNFRSF4, TNFRSF9, TNFSF10, TNFSF13B, TNFSF13B, TNFSF15, TNIP1, TNIP3, TP53, TRAF1, TRAF2, TREM1, TRPC1, TWIST1, UBE2M, UCP2, UGCGL1, UPK1B, UPP1, VCAM1, VEGFC, VIM, VPS53, WNT10B, WT1, XDH, XIAP, YY1, and ZNF366. In one embodiment, Compound 8 decreases the expression of one or more NFκB-associated genes found to be elevated in the subject, and / or increases the expression of one or more NFκB- associated genes found to be decreased in the subject. In one embodiment, Compound 8 decreases the expression of one or more NFκB-associated genes found to be elevated in the subject before the administration of Compound 8, and / or increases the expression of one or more DB1 / 147901903.2 38 NFκB-associated genes found to be decreased in the subject before the administration of Compound 8. In one embodiment, Compound 8 decreases the expression of one or more NFκB- associated genes found to be elevated in the subject compared to a healthy control subject, and / or increases the expression of one or more NFκB-associated genes found to be decreased in the subject compared to a healthy control subject. In one embodiment, Compound 8 decreases the expression of one or more NFκB-associated genes selected from: A4, ABCA1, ABCB1, ABCB4, ABCB9, ABCC6, ABCG5, ABCG8, ADAM19, ADH1A, ADORA1, ADORA2A, ADRA2B. AFP, AGER, AGT, AHCTF1, AICDA, AKR1C1, ALOX12, ALOX5, AMACR, AMH, ANGPT1, APOBEC2, APOC3, APOD, APOE, AQP4, AR, ARFRP1, ART1, ASPH, ASS1, ATP1A2, B2M, BACE1, BAX, BCL2, BCL2A1, BCL2L1, BCL2L11, BCL3, BDKRB1, BDKRB1, BDNF, BGN, BLIMP1 / PRDM1, BLNK, BLR1, BMI1, BMP2, BMP4, BNIP3, BRCA2, BTK, C3, C4A, C4BPA, C69, CALCB, CASP4, CAV1, CCL1, CCL15, CCL17, CCL19, CCL2, CCL20, CCL22, CCL23, CCL28, CCL3, CCL4, CCL5, CCND1, CCND2, CCND3, CCR5, CCR7, CD209, CD274, CD38, CD3G, CD40, CD40LG, CD44, CD48, CD54, CD80, CD83, CD86, CDK6, CDKN1A, CDX1, CEBPD, CFB, CFLAR, CGM3, CHI3L1, CIDEA, CLDN2, COL1A2, CR2, CREB3, CRP, CSF1, CSF2, CSF3, CTSB, CTSL1, CXCL1, CXCL10, CXCL11, CXCL3, CXCL5, CXCL6, CXCL9, CYP19A1, CYP27B1, CYP2C11, CYP2E1, CYP7B1, DCTN4, DEFB2, DIO2, DMP1, DNASE1L2, DPYD, DUSP1, E2F3, EBI3, EDN1, EGFR, EGR1, ELF3, ENG, ENO2, EPHA1, EPO, ERBB2, ERVWE1, F11R, F3, F8, FABP6, FAM148A, FAS, FASLG, FCER2. FCER2 / CD23, FCGRT, FGF8, FN1, FOS, FSTL3, FTH1, G6PC, G6PD, GAD1, GADD45B, GATA3, GBP1, GCLC, GCLM, GCNT1, GJB1, GNAI2, GNB2L1, GNRH2, GRIN1, GRIN2A, GRM2, GRO-beta, GRO-gamma, GSTP1, GUCY1A2, GZMB, HAMP, HAS1, HBE1, HBZ, HGF, HIF1A, HLA-B, HLA-G, HMGN1, HMOX1, HOXA9, HPSE, HSD11B2, HSD17B8, HSP90AA1, ICOS, IDO1, IER2, IER3, IFI44L, IFNB, IFNG, IGFBP1, IGFBP2, IGHE, IGHG1, IGHG2, IGHG4, IGKC, Iigp1, IL10, IL11, IL12A, IL12B, IL13, IL15, IL17, IL1A, IL1B, IL1RN, IL2, IL23A, IL27, IL2RA, IL6, IL8, IL8RA, IL8RB, IL9, INHBA, IRF1, IRF2, IRF4, IRF7, JMJD3, JUNB, KC, KCNK5, KCNN2, KISS1, KITLG, KLF10, KLK3, KLRA1, KRT15, KRT3, KRT5, KRT6B, LAMB2, LBP, LCN2, LEF1, LGALS3, LIPG, LTA, LTB, LTF, LYZ, MADCAM1, MAP4K1, MBP, MDK, MMP1, MMP3, MMP9, MT3, MTHFR, MUC2, MX1, MYB, MYC, MYLK, MYOZ1, NCAM, NFKB1, NFKB2, NFKBIA, NFKBIE, NFKBIZ, NGFB, NK4, NLRP2, NOD2, NOS1, DB1 / 147901903.2 39 NOS2A, NOX1, NPY1R, NQO1, NR3C1, NR4A2, NRG1, NUAK2, OLR1, OPN1SW, OPRD1, OPRM1, ORM1, Osterix, OXTR, PAFAH2, PAX8, PDE7A, PDGFB, PDYN, PENK, PGK1, PGLYRP1, PGR, PI3KAP1, PIGF, pIgR, PIK3CA, PIM1, PLA2, PLAU, PLCD1, PLK3, POMC, PPARGC1B, PPP5C, PRF1, PRKACA, PRKCD, PRL, PSMB9, PSME1, PSME2, PTAFR,, PTEN, PTGDS, PTGES, PTGIS, PTGS2, PTHLH, PTPN1, PTPN13, PTS, PTX3, PYCARD, RAG1, RAG2, RBBP4, Rdh1, Rdh7, REL, RELB, REV3L, RIPK2, S100A10, S100A4, S100A6, SAA1, SAA2, SAA, SAT1, SCNN1A, SDC4, SELE, SELP, SELS, SENP2, SERPINA1, SERPINA2, SERPINA3, SERPINB1, SERPINE1, PAI-1, SERPINE2, SH3BGRL, SKALP, PI3, SKP2, SLC11A2, SLC16A1, SLC3A2, SLC6A6, Slfn2, SNAI1, SOD1, SOD2, SOX9, SPATA19, SPI1, SPP1, ST6GAL1, ST8SIA1, STAT5A, SUPV3L1, TACR1, TAP1, TAPBP, TCRB, TERT, TF, TFEC, TFF3, TFPI2, TGM1, TGM2, THBS1, THBS2, TICAM1, TIFA, TLR2, TLR9, TNC, TN, TNFAIP2, TNFAIP3, TNFRSF1B, TNFRSF4, TNFRSF9, TNFSF10, TNFSF13B, TNFSF13B, TNFSF15, TNIP1, TNIP3, TP53, TRAF1, TRAF2, TREM1, TRPC1, TWIST1, UBE2M, UCP2, UGCGL1, UPK1B, UPP1, VCAM1, VEGFC, VIM, VPS53, WNT10B, WT1, XDH, XIAP, YY1, and ZNF366 in the subject. In one embodiment, Compound 8 increases the expression of one or more NFκB-associated genes selected from: A4, ABCA1, ABCB1, ABCB4, ABCB9, ABCC6, ABCG5, ABCG8, ADAM19, ADH1A, ADORA1, ADORA2A, ADRA2B. AFP, AGER, AGT, AHCTF1, AICDA, AKR1C1, ALOX12, ALOX5, AMACR, AMH, ANGPT1, APOBEC2, APOC3, APOD, APOE, AQP4, AR, ARFRP1, ART1, ASPH, ASS1, ATP1A2, B2M, BACE1, BAX, BCL2, BCL2A1, BCL2L1, BCL2L11, BCL3, BDKRB1, BDKRB1, BDNF, BGN, BLIMP1 / PRDM1, BLNK, BLR1, BMI1, BMP2, BMP4, BNIP3, BRCA2, BTK, C3, C4A, C4BPA, C69, CALCB, CASP4, CAV1, CCL1, CCL15, CCL17, CCL19, CCL2, CCL20, CCL22, CCL23, CCL28, CCL3, CCL4, CCL5, CCND1, CCND2, CCND3, CCR5, CCR7, CD209, CD274, CD38, CD3G, CD40, CD40LG, CD44, CD48, CD54, CD80, CD83, CD86, CDK6, CDKN1A, CDX1, CEBPD, CFB, CFLAR, CGM3, CHI3L1, CIDEA, CLDN2, COL1A2, CR2, CREB3, CRP, CSF1, CSF2, CSF3, CTSB, CTSL1, CXCL1, CXCL10, CXCL11, CXCL3, CXCL5, CXCL6, CXCL9, CYP19A1, CYP27B1, CYP2C11, CYP2E1, CYP7B1, DCTN4, DEFB2, DIO2, DMP1, DNASE1L2, DPYD, DUSP1, E2F3, EBI3, EDN1, EGFR, EGR1, ELF3, ENG, ENO2, EPHA1, EPO, ERBB2, ERVWE1, F11R, F3, F8, FABP6, FAM148A, FAS, FASLG, FCER2. FCER2 / CD23, FCGRT, FGF8, FN1, FOS, FSTL3, FTH1, G6PC, G6PD, GAD1, GADD45B, GATA3, GBP1, GCLC, DB1 / 147901903.2 40 GCLM, GCNT1, GJB1, GNAI2, GNB2L1, GNRH2, GRIN1, GRIN2A, GRM2, GRO-beta, GRO-gamma, GSTP1, GUCY1A2, GZMB, HAMP, HAS1, HBE1, HBZ, HGF, HIF1A, HLA-B, HLA-G, HMGN1, HMOX1, HOXA9, HPSE, HSD11B2, HSD17B8, HSP90AA1, ICOS, IDO1, IER2, IER3, IFI44L, IFNB, IFNG, IGFBP1, IGFBP2, IGHE, IGHG1, IGHG2, IGHG4, IGKC, Iigp1, IL10, IL11, IL12A, IL12B, IL13, IL15, IL17, IL1A, IL1B, IL1RN, IL2, IL23A, IL27, IL2RA, IL6, IL8, IL8RA, IL8RB, IL9, INHBA, IRF1, IRF2, IRF4, IRF7, JMJD3, JUNB, KC, KCNK5, KCNN2, KISS1, KITLG, KLF10, KLK3, KLRA1, KRT15, KRT3, KRT5, KRT6B, LAMB2, LBP, LCN2, LEF1, LGALS3, LIPG, LTA, LTB, LTF, LYZ, MADCAM1, MAP4K1, MBP, MDK, MMP1, MMP3, MMP9, MT3, MTHFR, MUC2, MX1, MYB, MYC, MYLK, MYOZ1, NCAM, NFKB1, NFKB2, NFKBIA, NFKBIE, NFKBIZ, NGFB, NK4, NLRP2, NOD2, NOS1, NOS2A, NOX1, NPY1R, NQO1, NR3C1, NR4A2, NRG1, NUAK2, OLR1, OPN1SW, OPRD1, OPRM1, ORM1, Osterix, OXTR, PAFAH2, PAX8, PDE7A, PDGFB, PDYN, PENK, PGK1, PGLYRP1, PGR, PI3KAP1, PIGF, pIgR, PIK3CA, PIM1, PLA2, PLAU, PLCD1, PLK3, POMC, PPARGC1B, PPP5C, PRF1, PRKACA, PRKCD, PRL, PSMB9, PSME1, PSME2, PTAFR,, PTEN, PTGDS, PTGES, PTGIS, PTGS2, PTHLH, PTPN1, PTPN13, PTS, PTX3, PYCARD, RAG1, RAG2, RBBP4, Rdh1, Rdh7, REL, RELB, REV3L, RIPK2, S100A10, S100A4, S100A6, SAA1, SAA2, SAA, SAT1, SCNN1A, SDC4, SELE, SELP, SELS, SENP2, SERPINA1, SERPINA2, SERPINA3, SERPINB1, SERPINE1, PAI-1, SERPINE2, SH3BGRL, SKALP, PI3, SKP2, SLC11A2, SLC16A1, SLC3A2, SLC6A6, Slfn2, SNAI1, SOD1, SOD2, SOX9, SPATA19, SPI1, SPP1, ST6GAL1, ST8SIA1, STAT5A, SUPV3L1, TACR1, TAP1, TAPBP, TCRB, TERT, TF, TFEC, TFF3, TFPI2, TGM1, TGM2, THBS1, THBS2, TICAM1, TIFA, TLR2, TLR9, TNC, TN, TNFAIP2, TNFAIP3, TNFRSF1B, TNFRSF4, TNFRSF9, TNFSF10, TNFSF13B, TNFSF13B, TNFSF15, TNIP1, TNIP3, TP53, TRAF1, TRAF2, TREM1, TRPC1, TWIST1, UBE2M, UCP2, UGCGL1, UPK1B, UPP1, VCAM1, VEGFC, VIM, VPS53, WNT10B, WT1, XDH, XIAP, YY1, and ZNF366 in the subject. In another aspect, the present disclosure provides a method of determining whether a subject with a disease or disorder selected from an inflammatory disease or disorder, or a cancer selected from acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), can be treated by the administration of Compound 8 or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, the method comprising: determining whether the subject has DB1 / 147901903.2 41 an elevated secretion of one or more cytokines selected from: TNF-α, IL-1 β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, IL-23, GM-CSF, and IFN-γ. In one embodiment, the subject has elevated expression of one or more cytokines compared to a healthy control subject and / or a decreased expression of one or more cytokines compared to a healthy control subject. In one embodiment, any of the methods described above further comprise administering to the subject Compound 8: or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof. In one embodiment, the inflammatory disease or disorder is selected from chronic inflammation, sepsis, rheumatoid arthritis, hidradenitis suppurativa, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, psoriasis, Sjögren’s syndrome, Ankylosing spondylitis, systemic sclerosis, Type 1 diabetes mellitus, Crohn’s disease, atopic dermatitis, and colitis. In one embodiment, the AML is relapsed AML, refractory AML, relapsed / refractory AML, AML with resistance to hypomethylating agents, AML with resistance to venetoclax, AML with resistance to hypomethylating agents and venetoclax, monocytic AML, or monocytic-like AML, optionally wherein the subject has AML and the subject has a gene mutation in one or more of FLT3, TET2, KIT, BCOR, BRAF, CDKN2A, UTX, ZRSR2, NPM1, PTEN, DNMT3A, EZH2, RUNX1, JAK2, ASXL1, ABL1, ATRX, BCORL1, KDM6A, PTPN11, TP53, CBL, CEBPA, FBXW7, HRAS, NRAS, IDH1, IDH2, NRAS, PDGFRA, SF3B1, ETV6, PHF6, GNAS, KRAS, NOTCH1, STAG2, SETBP1, GATA1, GATA2, WT1, SRSF2, GNAS, CEBPA, CALR, MPL, BCL11A, ATM, CTCF, U2AF1, TYK2, FBX, RUI, RAD21, or MLL3; and / or the MDS is MDS with a splicing factor mutation, MDS with a mutation in isocitrate dehydrogenase 1, or MDS with a mutation in isocitrate dehydrogenase 2, optionally wherein the subject has MDS and has a gene mutation in U2AF1, FLT3, ASXL1, BCORL1, BRAF, CBL, CDKN2A, DNMT3A, FBXW7, GATA2, IDH2, KRAS, NOTCH1, NRAS, PDGFRA, PTEN, PTPN11, TET2, TP53, EZH2, HRAS, KIT, MPL, PHF6, RUNX1, WT1, ABL1, CEBPA, ETV6, IDH2, KDM6A, KIT, DB1 / 147901903.2 42 KRAS, PTEN, RUNX1, SF3B1, or ZRSR2; and / or optionally wherein the MDS with a splicing factor mutation comprises MDS with a splicing factor mutation in U2AF1, SRSF2, SF3B1, or ZRSR2. In one embodiment, Compound 8 has an IRAK1 IC50of less than about 40 nM, optionally an IRAK4 IC50 of less than about 5 nM, and / or an FLT3 IC50 of less than about 2.5 nM. In one embodiment, Compound 8 has IRAK4:IRAK1 inhibitory potency ratio of less than about 40. In one embodiment, Compound 8 is more effective at inhibiting cancer cell colony formation and / or cancer progenitor cell function when compared to a compound which inhibits IRAK1 without inhibiting IRAK4 or inhibits IRAK4 without inhibiting IRAK1. In one embodiment, Compound 8 provides sustained treatment of the inflammatory disease / disorder, AML, or MDS in the subject, optionally wherein the sustained treatment is greater than the treatment provided from a compound which inhibits IRAK1 without inhibiting IRAK4 or inhibits IRAK4 without inhibiting IRAK1. In one embodiment, in any of the methods described above, the administration of Compound 8 comprises parenteral administration, mucosal administration, intravenous administration, subcutaneous administration, topical administration, intradermal administration, oral administration, sublingual administration, intranasal administration, or intramuscular administration; and / or Compound 8 is administered to the subject in an amount of from about 0.005 mg / kg subject body weight to about 1,000 mg / kg subject body weight; and / or Compound 8 is administered to the subject in a dosage of from about 0.35 mg to about 70,000 mg; and / or Compound 8 is administered to the subject daily, every other day, every third day, every fourth day, every fifth day, every sixth day, once a week, twice a month, or once a month. In one embodiment, in any of the methods described above, Compound 8 treats the inflammatory disease or disorder, or the cancer selected from AML and MDS, in the subject during the time period that the compound is administered to the subject. In one embodiment, in any of the methods described above, Compound 8 continues to treat the inflammatory disease or disorder, or the cancer selected from AML and MDS, in the subject after the administration is stopped, optionally Compound 8 continues to treat the inflammatory disease or disorder, or the cancer selected from AML and MDS, in the subject for about 1 day, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, about one week, about two weeks, about three weeks, or about a month after the administration is stopped. In one embodiment, in any of the methods described above, the method further comprises administering to the subject one or more of: a chemotherapy agent, a BCL2 inhibitor, an immune modulator, a DB1 / 147901903.2 43 BTK inhibitor, a DNA methyltransferase inhibitor / hypomethylating agent, an anthracycline, a histone deacetylase (HDAC) inhibitor, a purine nucleoside analogue (antimetabolite), an isocitrate dehydrogenase 1 or 2 (IDH1 and / or IDH2) inhibitor, an antibody-drug conjugate, an mAbs / immunotherapy, a Plk inhibitor, a MEK inhibitor, a CDK inhibitor, a CDK9 inhibitor, a CDK8 inhibitor, a retinoic acid receptor agonist, a TP53 activator, a CELMoD, a smoothened receptor antagonist, an ERK inhibitor including an ERK2 / MAPK1 or ERK1 / MAPK3 inhibitor, a PI3K inhibitor, an mTOR inhibitor, a steroid or glucocorticoid, a steroid or glucocorticoid receptor modulator, an EZH2 inhibitor, a hedgehog (Hh) inhibitor, a Topoisomerase I inhibitor, a Topoisomerase II inhibitor, an aminopeptidase / Leukotriene A4 hydrolase inhibitor, a FLT3 / Axl / ALK inhibitor, a FLT3 / KIT / PDGFR, PKC, and / or KDR inhibitor, a Syk inhibitor, an E-selectin inhibitor, an NEDD8-activator, an MDM2 inhibitor, a PLK1 inhibitor, an Aura A inhibitor, an aurora kinase inhibitor, an EGFR inhibitor, an AuroraB / C / VEGFR1 / 2 / 3 / FLT3 / CSF- 1R / Kit / PDGFRA / B inhibitor, an AKT 1, 2, and / or 3 inhibitor, a ABL1 / 2 / SRC / EPHA2 / LCK / YES1 / KIT / PDGFRB / FYN inhibitor, a farnesyltransferase inhibitor, a BRAF / MAP2K1 / MAP2K2 inhibitor, a Menin-KMT2A / MLL inhibitor, and a multikinase inhibitor; optionally comprising administering to the subject at least one of a BCL2 inhibitor, a BTK inhibitor, a glucocorticoid, a CDK inhibitor, and a DNA methyltransferase inhibitor. In one embodiment, the BCL2 inhibitor is venetoclax or a pharmaceutically acceptable salt thereof; and / or the BTK inhibitor is ibrutinib or acalabrutinib or a pharmaceutically acceptable salt of any one thereof; and / or the glucocorticoid is selected from dexamethasone, methylprednisolone, prednisolone or a pharmaceutically acceptable salt of any one thereof; and / or the CDK inhibitor is selected from CDK4 / 6 inhibitor Palbociclib, CDK7 inhibitor THZ1, and / or CDK9 inhibitors BAY1251152 and Atuveciclib, or a pharmaceutically acceptable salt of any one thereof; and / or the DNA methyltransferase inhibitor is azacitidine or a pharmaceutically acceptable salt thereof. In one embodiment, the combination of Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, and venetoclax, or a pharmaceutically acceptable salt thereof, increases survival of the subject; optionally the combination of Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, and venetoclax, or a pharmaceutically acceptable salt thereof, increases survival of the subject compared to a subject administered either Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, or venetoclax, or a pharmaceutically acceptable salt thereof; DB1 / 147901903.2 44 optionally wherein the combination of Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, and venetoclax, or a pharmaceutically acceptable salt thereof, increases survival of the subject by about 10% to 200%, about 10% to 175%, about 20% to 175%, or about 20% to 150% compared to the subject administered either Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, or venetoclax, or a pharmaceutically acceptable salt thereof. BRIEF DESCRIPTION OF THE DRAWINGS FIG.1 depicts that the NFkB potency of Compounds 1-13, Compound 15, and comparative compounds correlates with their IRAK1 potency. FIG.2 depicts that the NFkB potency of Compounds 1-13, Compound 15, and comparative compounds correlates with their IRAK4 potency. FIG.3 depicts colony forming assays demonstrating that the NFkB potency of Compounds 1-13 and Compound 15 correlates with their MDSL CFC potency. FIG.4 depicts colony forming assays demonstrating that the NFkB potency of Compounds 1-13 and Compound 15 correlates with their THP-1 CFC potency. FIG.5 depicts the kinase profile of comparative compounds with their PAM and IL1β IC50. FIG.6A depicts Compound 14 and Compound 15. FIG.6B depicts the kinase profile of Compound 14 and Compound 15 with their PAM and IL1β IC50. FIG.7 depicts the kinase profile of Compound 2, Compound 7, and Compound 8 with their PAM and IL1β IC50. FIGS.8A-8B depict the MS methods used in Example 2. The MS is the standard curve quantitation values demonstrating the range of quants applicable from the qualified assay using recombinant proteins assessed via the method. FIG.8A depicts IRAK1 / 4 expression analysis by IP-MS. FIG.8B depicts hybrid LCMS. FIG.9 demonstrates that Compound 8 is a highly potent and selective IRAK1 / IRAK4 / panFLT3 inhibitor. FIG.10 demonstrates that dual IRAK1 / 4 inhibition drives NF-κB signaling, wherein complete antagonism of signaling through both receptor pathways is only seen with the IRAK1 / 4 inhibitor Compound 8. DB1 / 147901903.2 45 FIGS.11A-11C demonstrate that Compound 8 suppresses NF-κB and IRAK1 / 4- dependent signaling in AML cells. FIG.11A is a principal component analysis (PCA) plot showing the variation between the samples in THP-1 cells. FIG.11B is a plot depicting the relative expression of NF-κB target genes by their Z-score (blue downregulated genes, red upregulated genes). FIG.11C is a plot depicting the relative expression of IRAK1 / 4 dependency genes by their Z-score (blue downregulated genes, red upregulated genes). FIG.12 is a chart depicting differentially expressed genes (DEGs) for different concentrations of Compound 8 and CA-4948 (emavusertib) calculated by comparison against control samples. FIGS.13A-13C are charts of DEGs versus drug concentration. FIG.13A is a chart of control versus 1 µM Compound 8 DEGs. FIG.13B is a chart of control versus 5 µM Compound 8 DEGs. FIG 13C is a chart of control versus 10 µM CA-4948 DEGs. FIGS.14A-14C provides charts and Venn diagrams of common DEGs for different drugs / concentrations. FIG.14A is a chart and Venn diagram of common DEGs between 10 µM CA-4948 and 1 µM Compound 8. FIG.14B is a chart and Venn diagram of common DEGs between 10 µM CA-4948 and 5 µM Compound 8. FIG.14C is a chart and Venn diagram of common DEGs between 1 µM Compound 8 and 5 µM Compound 8. FIGS.15A-15B provide canonical NF-κB target genes. FIG.15A is a chart of canonical NfκB target genes for different concentrations of Compound 8 and CA-4948. FIG.15B is a plot of control versus 5 µM Compound 8 canonical NF-κB target genes. FIGS.16A-16B provide signature genes on Compound 8 (by fold change). FIG.16A is a chart of signature genes for different concentrations of Compound 8 and CA-4948. FIG.16B is a plot of control versus 5 µM Compound 8. FIG.17 depicts the short IRAK1 / 4 gene signature for Compound 8 (by Z-score). FIG.18 is a chart of FLT3 wildtype THP-1 (left) and MDSL (right) cultured cells treated with DMSO and different concentrations of CA-4948 or Compound 8. FIGS.19A-19F demonstrate that Compound 8 impairs leukemic colony formation in FLT3 wild type primary patient cells. FIG.19A depicts colony formation data in FLT3 wild type AML(33766) patient cells. FIG.19B depicts colony formation data in FLT3 wild type MDS(3328) patient cells. FIG.19C depicts colony formation data in FLT3 wild type AML(2702) patient cells. FIG.19D depicts colony formation data in FLT3 wild type DB1 / 147901903.2 46 AML(3438) patient cells. FIG.19E depicts colony formation data in FLT3 wild type AML(2456) patient cells. FIG.19F depicts colony formation data in FLT3 wild type AML(2239) patient cells. FIG.20 is a chart of FLT3 mutant MOLM14 (D835Y) cultured cells treated with DMSO and different concentrations of gilteritinib, CA-4948 or Compound 8. FIGS.21A-21B demonstrate that Compound 8 impairs leukemic colony formation in FLT3 mutant primary patient cells. FIG.21A depicts colony formation data in FLT3 mutant AML(3930) patient cells. FIG.21B depicts colony formation data in FLT3 mutant AML(2228) patient cells. FIGS.22A-22B depict the creation of an IRAK1 / 4 signature (FIG.22A) and the analysis of the IRAK1 / 4 signature in patients (FIG.22B). FIGS.23A-23I depict the analysis of primary AML blast colony forming assays of FLT3 wildtype patients. FIGS.24A-24G depict the analysis of primary AML blast colony forming assays of FLT3 mutant patients. FIGS.25A-25D demonstrate that Compound 8 potently inhibits leukemic stem cell progenitor function regardless of mutational status. FIG.25A is a comparison between % inhibition of colony formation at 200 nM of Compound 8 across primary patient samples that are either wildtype or mutant for FLT3. No significant difference in response to inhibitor was seen between WT and FLT3 mutant samples. FIG.25B is a CFU comparison (WT vs mutant) and provides an estimation plot showing no significant difference between the two populations. FIG.25C provides the statistical analysis for the data shown in FIG.25A and FIG.25B. FIG. 25D is a chart of the mutational status of the corresponding FLT3 WT patient AML primary bone marrow blasts. *Similar mutational profiles were seen in FLT3 mutant AML patient samples (data not shown). FIG.26 provides a graph and a table demonstrating that the survival of an AML animal model is increased when the animal is treated with Compound 8 or venetoclax compared to a control animal. Survival is further increased when the animal is treated with a combination of Compound 8 and venetoclax. FIG.27 provides a graph demonstrating that Compound 8 prolongs survival in mice xenografted with MOLM14 FLT3-ITD (D835Y) compared to gilteritinib and CA-4948. DB1 / 147901903.2 47 FIGS.28A-28X demonstrate that Compound 8 inhibits innate and adaptive cytokine production. Healthy donor PBMCs were obtained for n=3 donors. To obtain this data, the cells were co-incubated for 48 hrs with stimulants + / - Compound 8 at 1 µM and 10 µM. Innate signaling stim is PAM3CSK4 at 10 ng / mL. Adaptive immune signaling stim is CD3-CD28 Dynabeads at 1:1 ratio (beads:cell). Crisaborole is a control inhibitor that inhibits most inflammatory cytokines. The supernatants were collected and analyzed for GM-CSF, IFNγ, IL- 1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70 (no changes), IL-13, IL-17A, IL-23, and TNFα. DETAILED DESCRIPTION The following related applications are incorporated by reference herein in their entirety, and for all purposes: International Publication No. WO 2018081738, TREATMENT OF DISEASES ASSOCIATED WITH ACTIVATED IRAK, filed October 30, 2017; U.S. Publication No.2021 / 0292843, TREATMENT OF DISEASES ASSOCIATED WITH ACTIVATED IRAK, filed April 4, 2019; International Publication No. WO 2014190163, Combination Therapy for MDS, filed May 22, 2014; U.S. Patent No.9,168,257, Combination Therapy for MDS, issued October 27, 2015; U.S. Patent No.9,504,706, Combination Therapy for MDS, issued November 29, 2016; U.S. Patent No.9,855,273, Combination Therapy for MDS, issued January 2, 2018; International Publication No. WO 2018038988, Compounds, Compositions, Methods for Treating Diseases, and Methods for Preparing Compounds, filed August 16, 2017; U.S. Patent No.11,254,667, Substituted imidazo[1,2-a]pyridines as IRAK 1 / 4 and FLT3 inhibitors, issued February 2, 2022; U.S. Publication No.2022 / 0213094, Substituted Imidazo[l,2-a]-pyridines as IRAK 1 / 4 and FLT3 Inhibitors, filed January 4, 2022; U.S. Publication No.2020 / 0199123, Substituted imidazo[1,2-a]pyridines as IRAK 1 / 4 and FLT3 inhibitors, filed February 28, 2020; U.S. Publication No.2022 / 0235042, Substituted Imidazo[l,2- a]-pyridines as IRAK 1 / 4 and FLT3 Inhibitors, filed January 28, 2022; International Publication No. WO 2020252487, Rational therapeutic targeting of oncogenic immune signaling states in myeloid malignancies via the ubiquitin conjugating enzyme UBE2N, filed June 15, 2020; International Publication No. WO 2022026935, Multi-Cyclic IRAK and FLT3 Inhibiting Compounds and Uses Thereof, filed July 31, 2021; International Publication No. WO 2022140647, Multi-Cyclic IRAK and FLT3 Inhibiting Compounds and Uses Thereof, filed December 23, 2021; International Publication No. WO 2023009833, Multi-Cyclic IRAK and DB1 / 147901903.2 48 FLT3 Inhibiting Compounds and Uses Thereof, filed July 29, 2022; International Patent Application No. PCT / US2023 / 068520, Multi-Cyclic IRAK and FLT3 Inhibiting Compounds and Uses Thereof, filed June 15, 2023; International Patent Application No. PCT / US2023 / 068897, Multi-Cyclic IRAK and FLT3 Inhibiting Compounds and Uses Thereof, filed June 22, 2023; International Patent Application No. PCT / US2023 / 071435, Multi-Cyclic IRAK and FLT3 Inhibiting Compounds and Uses Thereof, filed August 1, 2023; International Patent Application No. PCT / US2023 / 034438, Multi-Cyclic IRAK and FLT3 Inhibiting Compounds and Uses Thereof, filed October 4, 2023; U.S. Patent Application No.18 / 293,109, Multi-Cyclic IRAK and FLT3 Inhibiting Compounds and Uses Thereof, filed January 29, 2024; and International Patent Application No. PCT / US2024 / 014038, Multi-Cyclic IRAK and FLT3 Inhibiting Compounds and Uses Thereof, filed February 1, 2024. While embodiments encompassing the general disclosed concepts may take diverse forms, various embodiments will be described herein, with the understanding that the present disclosure is to be considered merely exemplary, and the general disclosed concepts are not intended to be limited to the disclosed embodiments. Some embodiments of the disclosure include disclosed compounds. Other embodiments include compositions (e.g., pharmaceutical compositions) comprising the disclosed compound. Still other embodiments of the disclosure include compositions for treating, for example, certain diseases using the disclosed compounds. Some embodiments include methods of using the disclosed compound (e.g., in compositions or in pharmaceutical compositions) for administering and treating. Further embodiments include methods for making the disclosed compound. Yet further embodiments include methods for determining whether a particular patient is likely to be responsive to such treatment with the disclosed compounds and compositions. Unless otherwise noted, terms are to be understood according to conventional usage by those of ordinary skill in the relevant art. The abbreviations used herein have their conventional meaning within the chemical and biological arts. The chemical structures and formulae set forth herein are constructed according to the standard rules of chemical valency known in the chemical arts. Where substituent groups are specified by their conventional chemical formulae, written from left to right, they equally encompass the chemically identical substituents that would result from writing the structure from right to left, e.g., -CH2O- is equivalent to -OCH2-. DB1 / 147901903.2 49 As used herein, in relation to the compounds of the disclosure, the term “attached” signifies a stable covalent bond, certain preferred points of attachment being apparent to those of ordinary skill in the art. As used herein (unless otherwise specified), the term “alkyl” means a monovalent, straight or branched hydrocarbon chain, which can be fully saturated, mono- or polyunsaturated and can include di- and multivalent radicals, having the number of carbon atoms designated (i.e., C1-C10means one to ten carbons). For example, the terms “C1-C7alkyl” or “C1-C4alkyl” refer to straight- or branched-chain saturated hydrocarbon groups having from 1 to 7 (e.g., 1, 2, 3, 4, 5, 6, or 7), or 1 to 4 (e.g., 1, 2, 3, or 4), carbon atoms, respectively. Examples of C1-C7alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, n- pentyl, s-pentyl, n-hexyl, and n-septyl. Examples of C1-C4 alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, and t-butyl. As used herein (unless otherwise specified), the term “alkenyl” means a monovalent, straight or branched hydrocarbon chain that includes one or more (e.g., 1, 2, 3, or 4) double bonds. Double bonds can occur in any stable point along the chain and the carbon-carbon double bonds can have either the cis or trans configuration. For example, this definition shall include but is not limited to ethenyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, 1,5-octadienyl, 1,4,7-nonatrienyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, ethylcyclohexenyl, butenylcyclopentyl, l-pentenyl-3-cyclohexenyl, and the like. Similarly, “heteroalkenyl” refers to heteroalkyl having one or more double bonds. Further examples of alkenyl groups include, but are not limited to, vinyl, allyl, 1-propenyl, 2- propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1- hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, and 5-hexenyl. As used herein (unless otherwise specified), the term “alkynyl” means a monovalent, straight or branched hydrocarbon chain that includes one or more (e.g., 1, 2, 3, or 4) triple bonds and that also may optionally include one or more (e.g.1, 2, 3, or 4) double bonds in the chain. Examples of alkynyl groups include, but are not limited to, ethynyl, 1-propynyl, 2-propynyl, 1- butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-hexynyl, 2- hexynyl, 3-hexynyl, 4-hexynyl, and 5-hexynyl. As used herein (unless otherwise specified), the term “alkoxy” means any of the above alkyl, alkenyl, or alkynyl groups which is attached to the remainder of the molecule by an DB1 / 147901903.2 50 oxygen atom (alkyl-O-). Examples of alkoxy groups include, but are not limited to, methoxy (sometimes shown as MeO-), ethoxy, isopropoxy, propoxy, and butyloxy. The term “alkylene,” by itself or as part of another substituent, means, unless otherwise stated, a divalent radical derived from an alkyl, alkenyl, or alkynyl group, as exemplified, but not limited by, -CH2CH2CH2CH2-. Typically, an alkyl (or alkylene) group will have from 1 to 24 carbon atoms, with those groups having 10 or fewer carbon atoms being preferred in the compounds disclosed herein. A “lower alkyl” or “lower alkylene” is a shorter chain alkyl or alkylene group, generally having eight or fewer carbon atoms. As used herein (unless otherwise specified), the term “cycloalkyl” means a monovalent, monocyclic or bicyclic, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 membered hydrocarbon group. The rings can be saturated or partially unsaturated. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, and bicycloalkyls (e.g., bicyclooctanes such as [2.2.2]bicyclooctane or [3.3.0]bicyclooctane, bicyclononanes such as [4.3.0]bicyclononane, and bicyclodecanes such as [4.4.0]bicyclodecane (decalin), or spiro compounds). For a monocyclic cycloalkyl, the ring is not aromatic. For a bicyclic cycloalkyl, if one ring is aromatic, then the other is not aromatic. For a bicyclic cycloalkyl, one or both rings can be substituted. The term “heteroalkyl,” by itself or in combination with another term, means, unless otherwise stated, a stable straight or branched chain, or combinations thereof, consisting of at least one carbon atom and at least one heteroatom selected from the group consisting of O, N, P, Si, and S, and wherein the nitrogen and sulfur atoms can optionally be oxidized, and the nitrogen heteroatom can optionally be quaternized. The heteroatom(s) O, N, P, S, and Si can be placed at any interior position of the heteroalkyl group or at the position at which the alkyl group is attached to the remainder of the molecule. Examples include, but are not limited to: -CH2-CH2-O-CH3, -CH2-CH2-NH-CH3, -CH2-CH2-N(CH3)-CH3, -CH2-S-CH2-CH3, -CH2-CH 2, -S(O)-CH3, -CH2-CH2-S(O)2-CH3, -CH=CH-O-CH3, -Si(CH3)3, -CH2-CH=N-OCH3, -CH=CH- N(CH3)-CH3, -O-CH3, -O-CH2-CH3, and -CN. Up to two heteroatoms can be consecutive, such as, for example, -CH2-NH-OCH3. Similarly, the term “heteroalkylene,” by itself or as part of another substituent, means, unless otherwise stated, a divalent radical derived from heteroalkyl, as exemplified, but not limited by, -CH2-CH2-S-CH2-CH2- and -CH2-S-CH2-CH2-NH-CH2-. For heteroalkylene groups, DB1 / 147901903.2 51 heteroatoms can also occupy either or both of the chain termini (e.g., alkyleneoxy, alkylenedioxy, alkyleneamino, alkylenediamino, and the like). Still further, for alkylene and heteroalkylene linking groups, no orientation of the linking group is implied by the direction in which the formula of the linking group is written. For example, the formula -C(O)2R'- represents both -C(O)2R'- and -R'C(O)2-. As described above, heteroalkyl groups, as used herein, include those groups that are attached to the remainder of the molecule through a heteroatom, such as -C(O)R', -C(O)NR', -NR'R'', -OR', -SR', and / or -SO2R'. Where “heteroalkyl” is recited, followed by recitations of specific heteroalkyl groups, such as -NR'R'' or the like, it will be understood that the terms heteroalkyl and -NR'R'' are not redundant or mutually exclusive. Rather, the specific heteroalkyl groups are recited to add clarity. Thus, the term “heteroalkyl” should not be interpreted herein as excluding specific heteroalkyl groups, such as -NR'R'' or the like. As used herein (unless otherwise specified), the term “halogen” or “halo” means monovalent Cl, F, Br, or I. Additionally, terms such as “haloalkyl” are meant to include monohaloalkyl and polyhaloalkyl. For example, the term “halo(C1-C4)alkyl” includes, but is not limited to, fluoromethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, 4-chlorobutyl, 3- bromopropyl, and the like. As used herein (unless otherwise specified), the term “aryl” means a monovalent, monocyclic or bicyclic, 5, 6, 7, 8, 9, 10, 11, or 12 member aromatic hydrocarbon group and also means polyunsaturated, aromatic, hydrocarbon substituent, which can be a single ring or multiple rings (preferably from 1 to 3 rings) that are fused together (i.e., a fused ring aryl) or linked covalently. A fused ring aryl refers to multiple rings fused together wherein at least one of the fused rings is an aryl ring. Examples of aryl groups include, but are not limited to, phenyl, naphthyl, tolyl, and xylyl. For an aryl that is bicyclic, one or both rings can be substituted. As used herein (unless otherwise specified), the term “heteroaryl” means a monovalent, monocyclic or bicyclic, 5, 6, 7, 8, 9, 10, 11, or 12 membered, hydrocarbon group, where 1, 2, 3, 4, 5, or 6 carbon atoms are replaced by a hetero atom independently selected from nitrogen, oxygen, or sulfur atom, and the monocyclic or bicyclic ring system is aromatic. Heteroaryl groups (or rings) can contain from one to four heteroatoms selected from N, O, and S, wherein the nitrogen and sulfur atoms are optionally oxidized, and the nitrogen atom(s) are optionally quaternized. Thus, the term “heteroaryl” includes fused ring heteroaryl groups (i.e., multiple DB1 / 147901903.2 52 rings fused together wherein at least one of the fused rings is a heteroaromatic ring). A 5,6-fused ring heteroarylene refers to two rings fused together, wherein one ring has 5 members and the other ring has 6 members, and wherein at least one ring is a heteroaryl ring. Likewise, a 6,6- fused ring heteroarylene refers to two rings fused together, wherein one ring has 6 members and the other ring has 6 members, and wherein at least one ring is a heteroaryl ring. And a 6,5-fused ring heteroarylene refers to two rings fused together, wherein one ring has 6 members and the other ring has 5 members, and wherein at least one ring is a heteroaryl ring. A heteroaryl group can be attached to the remainder of the molecule through a carbon or heteroatom. Examples of heteroaryl groups include, but are not limited to, thienyl (or thiophenyl), furyl, indolyl, pyrrolyl, pyridinyl, pyrazinyl, oxazolyl, thiaxolyl, quinolinyl, pyrimidinyl, imidazolyl, triazolyl, tetrazolyl, 1H-pyrazol-4-yl, 1-Me-pyrazol-4-yl, pyridin-3-yl, pyridin-4-yl, 3,5-dimethylisoxazolyl, 1H- pyrrol-3-yl, 3,5-di-Me-pyrazolyl, and 1H-pyrazol-4-yl. For a bicyclic heteroaryl, if one ring is aryl, then the other is heteroaryl. For a bicyclic heteroaryl, one or both rings can have one or more hetero atoms. For a bicyclic heteroaryl, one or both rings can be substituted. An “arylene” and a “heteroarylene,” alone or as part of another substituent, mean a divalent radical derived from an aryl and heteroaryl, respectively. Accordingly, the term "aryl" can represent an unsubstituted, mono-, di- or trisubstituted monocyclic, polycyclic, biaryl and heterocyclic aromatic groups covalently attached at any ring position capable of forming a stable covalent bond, certain preferred points of attachment being apparent to those skilled in the art (e. g.3-indolyl, 4-imidazolyl). The aryl substituents are independently selected from the group consisting of halo, nitro, cyano, trihalomethyl, C1-16alkyl, arylC1-16alkyl, C0-16alkyloxyC0-16alkyl, arylC0-16alkyloxyC0-16alkyl, C0-16alkylthioC0-16alkyl, arylC0-16alkylthioC0-16alkyl, C0- 16alkylaminoC0-16alkyl, arylC0-16alkylaminoC0-16alkyl, di(arylC1-16alkyl)aminoC0-16alkyl, C1- 16alkylcarbonylC0-16alkyl, arylC1-16alkylcarbonylC0-16alkyl, C1-16alkylcarboxyC0-16alkyl, arylC1- 16alkylcarboxyC0-16alkyl, C1-16alkylcarbonylaminoC0-16alkyl, arylC1-16alkylcarbonylaminoC0- 16alkyl,-C0-16alkylCOOR4, -C0-16alkylCONR5R6wherein R4, R5and R6are independently selected from hydrogen, C1-C11alkyl, arylC0-C11alkyl, or R5 and R6 are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with or without one C1-16alkyl, arylC0-C16alkyl, or C0-Cl16alkylaryl substituent. Aryl includes but is not limited to pyrazolyl and triazolyl. DB1 / 147901903.2 53 For brevity, the term “aryl” when used in combination with other terms (e.g., aryloxy, arylthioxy, arylalkyl) includes both aryl and heteroaryl rings as defined above. Thus, the terms “arylalkyl,” “aralkyl” and the like are meant to include those radicals in which an aryl group is attached to an alkyl group (e.g., benzyl, phenethyl, pyridylmethyl, and the like) including those alkyl groups in which a carbon atom (e.g., a methylene group) has been replaced by, for example, an oxygen atom (e.g., phenoxymethyl, 2-pyridyloxymethyl, 3-(1-naphthyloxy)propyl, and the like), or a sulfur atom. Accordingly, the terms "arylalkyl" and the like (e.g. (4- hydroxyphenyl)ethyl, (2-aminonaphthyl)hexyl, pyridylcyclopentyl) represents an aryl group as defined above attached through an alkyl group as defined above having the indicated number of carbon atoms. The terms “cycloalkyl” and “heterocycloalkyl”, also referred to as “heterocyclyl”, by themselves or in combination with other terms, mean, unless otherwise stated, cyclic versions of “alkyl” and “heteroalkyl,” respectively. Examples of cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 1-cyclohexenyl, 3-cyclohexenyl, cycloheptyl, and the like. As used herein (unless otherwise specified), the term “heterocycloalkyl” or “heterocyclyl” means a monovalent, monocyclic or bicyclic, 5, 6, 7, 8, 9, 10, 11, or 12 membered, hydrocarbon, where 1, 2, 3, 4, 5, or 6 carbon atoms are replaced by a hetero atom independently selected from nitrogen atom, oxygen atom, or sulfur atom, and the monocyclic or bicyclic ring system is not aromatic. Additionally, for heterocycloalkyl, a heteroatom can occupy the position at which the heterocycle is attached to the remainder of the molecule. Examples of heterocycloalkyl include, but are not limited to, 1-(1,2,5,6- tetrahydropyridyl), 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-morpholinyl, 3-morpholinyl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothien-2-yl, tetrahydrothien-3-yl, 1-piperazinyl, 2-piperazinyl, tetrahydropyran, pyrolidinyl (e.g., pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, or pyrrolidin-4-yl), piperazinyl (e.g., piperazin-1-yl, piperazin-2-yl, piperazin-3- yl, or piperazin-4-yl), piperidinyl (e.g., piperadin-1-yl, piperadin-2-yl, piperadin-3-yl, or piperadin-4-yl), and morpholinyl (e.g., morpholin-1-yl, morpholin-2-yl, morpholin-3-yl, or morpholin-4-yl,). For a bicyclic heterocyclyl, if one ring is aromatic (e.g., monocyclic aryl or heteroaryl), then the other ring is not aromatic. For a bicyclic heterocyclyl, one or both rings can have one or more hetero atoms. For a bicyclic heterocyclyl, one or both rings can be substituted and the like. A “cycloalkylene” and a “heterocycloalkylene,” alone or as part of another DB1 / 147901903.2 54 substituent, means a divalent radical derived from a cycloalkyl and heterocycloalkyl, respectively. As used herein (unless otherwise specified), the term “hetero atom” means an atom selected from nitrogen atom, oxygen atom, or sulfur atom. As used herein (unless otherwise specified), the terms “hydroxy” or “hydroxyl” means a monovalent -OH group. The term “acyl” means, unless otherwise stated, -C(O)R where R is a substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. The term “oxo,” as used herein, means an oxygen that is double bonded to a carbon atom. The term “alkylsulfonyl,” as used herein, means a moiety having the formula -S(O2)-R', where R' is an alkyl group as defined above. R' can have a specified number of carbons (e.g., “C1-C4alkylsulfonyl”). The term "carbonyloxy" represents a carbonyl group attached through an oxygen bridge. In the above definitions, the terms "alkyl" and "alkenyl" can be used interchangeably in so far as a stable chemical entity is formed, as would be apparent to those skilled in the art. The term “linker” refers to attachment groups interposed between substituents. In some embodiments, the linker includes amido (-CONH-Rnor -NHCO-Rn), thioamido (-CSNH-Rnor -NHCS-Rn), carboxyl (-CO2-Rnor -OCORn), carbonyl (-CO-Rn), urea (-NHCONH-Rn), thiourea (-NHCSNH-Rn), sulfonamido (-NHSO2-Rnor -SO2NH-Rn), ether (-O-Rn), sulfonyl (-SO2-Rn), sulfoxyl (-SO-Rn), carbamoyl (-NHCO2-Rnor -OCONH-Rn), or amino (-NHRn) linking moieties. Each of the above terms (e.g., “alkyl,” “heteroalkyl,” “aryl,” and “heteroaryl”, and so forth) includes both substituted and unsubstituted forms of the indicated radical. Preferred substituents for each type of radical are provided herein. As used herein (unless otherwise specified), the term “substituted” (e.g., as in substituted alkyl) means that one or more hydrogen atoms of a chemical group (with one or more hydrogen atoms) can be replaced by one or more non-hydrogen substituents selected from the specified options. The replacement can occur at one or more positions. The term “optionally substituted” DB1 / 147901903.2 55 means that one or more hydrogen atoms of a chemical group (with one or more hydrogen atoms) can be, but is not required to be substituted. A “substituent group,” as used herein, means a non-hydrogen substituent group that may be, and preferably is, a group selected from the following moieties: (A) -NH2, -SH, -CN, -CF3, -NO2, halogen, hydroxy, oxo, -CN, methanoyl (-COH), carboxy (-CO2H), nitro (-NO2), -N(CH3)2, ethynyl (-CCH), propynyl, sulfo (-SO3H), CONH2, - CON(CH3)2, unsubstituted C1-C7alkyl, unsubstituted C1-C7heteroalkyl, unsubstituted C1-C7perfluorinated alkyl, unsubstituted C1-C7 alkoxy, unsubstituted C1-C7 haloalkoxy, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, unsubstituted heteroaryl, and (B) C1-C7alkyl, C1-C7heteroalkyl, C1-C7perfluorinated alkyl, C1-C7alkoxy, C1-C7haloalkoxy, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, substituted with at least one substituent selected from: (i) -NH2, -SH, -CN, -CF3, -NO2, halogen, hydroxy, oxo, -CN, methanoyl (-COH), carboxy (-CO2H), nitro (-NO2), -N(CH3)2, ethynyl (-CCH), propynyl, sulfo (-SO3H), CONH2, - CON(CH3)2, unsubstituted C1-C7 alkyl, unsubstituted C1-C7 heteroalkyl, unsubstituted C1-C7 perfluorinated alkyl, unsubstituted C1-C7alkoxy, unsubstituted C1-C7haloalkoxy, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, unsubstituted heteroaryl, and (ii) C1-C7 alkyl, C1-C7 heteroalkyl, C1-C7 perfluorinated alkyl, C1-C7 alkoxy, C1-C7 haloalkoxy, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, substituted with at least one substituent selected from: (a) -NH2, -SH, -CN, -CF3, -NO2, halogen, hydroxy, oxo, -CN, methanoyl (-COH), carboxy (-CO2H), nitro (-NO2), -N(CH3)2, ethynyl (-CCH), propynyl, sulfo (-SO3H), CONH2, - CON(CH3)2, unsubstituted C1-C7alkyl, unsubstituted C1-C7heteroalkyl, unsubstituted C1-C7perfluorinated alkyl, unsubstituted C1-C7 alkoxy, unsubstituted C1-C7 haloalkoxy, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, unsubstituted heteroaryl, and (b) C1-C7alkyl, C1-C7heteroalkyl, C1-C7perfluorinated alkyl, C1-C7alkoxy, C1-C7haloalkoxy, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, substituted with at least one substituent selected from: -NH2, -SH, -CN, -CF3, -NO2, halogen, hydroxy, oxo, -CN, methanoyl (-COH), carboxy (-CO2H), nitro (-NO2), -N(CH3)2, ethynyl (-CCH), propynyl, sulfo (-SO3H), CONH2, -CON(CH3)2, unsubstituted C1-C7alkyl, unsubstituted C1-C7heteroalkyl, unsubstituted C1-C7 perfluorinated alkyl, unsubstituted C1-C7 alkoxy, unsubstituted C1-C7 haloalkoxy, DB1 / 147901903.2 56 unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, unsubstituted heteroaryl. A “size-limited substituent” or “ size-limited substituent group,” as used herein, means a group, e.g., selected from all of the substituents described above for a “substituent group,” wherein each substituted or unsubstituted alkyl is a substituted or unsubstituted C1-C20 alkyl, each substituted or unsubstituted heteroalkyl is a substituted or unsubstituted 2-20-membered heteroalkyl, each substituted or unsubstituted cycloalkyl is a substituted or unsubstituted C4-C8cycloalkyl, and each substituted or unsubstituted heterocycloalkyl is a substituted or unsubstituted 4-8-membered heterocycloalkyl. A “lower substituent” or “lower substituent group,” as used herein, means a group, e.g., selected from all of the substituents described above for a “substituent group,” wherein each substituted or unsubstituted alkyl is a substituted or unsubstituted C1-C8 alkyl, each substituted or unsubstituted heteroalkyl is a substituted or unsubstituted 2-8-membered heteroalkyl, each substituted or unsubstituted cycloalkyl is a substituted or unsubstituted C5-C7 cycloalkyl, and each substituted or unsubstituted heterocycloalkyl is a substituted or unsubstituted 5-7-membered heterocycloalkyl. The term “about” used in the context of a numeric value indicates a range of + / - 10% of the numeric value, unless expressly indicated otherwise. Some compounds of the disclosure can have one or more chiral centers and can exist in and be isolated in optically active and racemic forms, for any of the one or more chiral centers. Some compounds can exhibit polymorphism. The compounds of the present disclosure (e.g., Formula I) encompass any optically active, racemate, stereoisomer form, polymorphism, or mixtures thereof. If a chiral center does not provide an indication of its configuration (i.e., R or S) in a chemical structure, it should be considered to represent R, S or a racemate. As used herein, the term “sample” encompasses a sample obtained from a subject or patient. The sample can be of any biological tissue or fluid. Such samples include, but are not limited to, sputum, saliva, buccal sample, oral sample, blood, serum, mucus, plasma, urine, blood cells (e.g., white cells), circulating cells (e.g. stem cells or endothelial cells in the blood), tissue, core or fine needle biopsy samples, cell-containing body fluids, free floating nucleic acids, urine, stool, peritoneal fluid, and pleural fluid, tear fluid, or cells therefrom. Samples can also include sections of tissues such as frozen or fixed sections taken for histological purposes or DB1 / 147901903.2 57 microdissected cells or extracellular parts thereof. A sample to be analyzed can be tissue material from a tissue biopsy obtained by aspiration or punch, excision or by any other surgical method leading to biopsy or resected cellular material. Such a sample can comprise cells obtained from a subject or patient. In some embodiments, the sample is a body fluid that include, for example, blood fluids, serum, mucus, plasma, lymph, ascitic fluids, gynecological fluids, or urine but not limited to these fluids. In some embodiments, the sample can be a non- invasive sample, such as, for example, a saline swish, a buccal scrape, a buccal swab, and the like. As used herein, “blood” can include, for example, plasma, serum, whole blood, blood lysates, and the like. As used herein, the term “assessing” includes any form of measurement, and includes determining if an element is present or not. The terms “determining,” “measuring,” “evaluating,” “assessing,” “analyzing,” and “assaying” can be used interchangeably and can include quantitative and / or qualitative determinations. As used herein, the term “monitoring” with reference to a type of cancer refers to a method or process of determining the severity or degree of the type of cancer or stratifying the type of cancer based on risk and / or probability of mortality. In some embodiments, monitoring relates to a method or process of determining the therapeutic efficacy of a treatment being administered to a patient. As used herein, “outcome” can refer to an outcome studied. In some embodiments, “outcome” can refer to survival / mortality over a given time horizon. For example, “outcome” can refer to survival / mortality over 1 month, 3 months, 6 months, 1 year, 5 years, or 10 years or longer. In some embodiments, an increased risk for a poor outcome indicates that a therapy has had a poor efficacy, and a reduced risk for a poor outcome indicates that a therapy has had a good efficacy. As used herein, the term “high risk clinical trial” refers to one in which the test agent has “more than minimal risk” (as defined by the terminology used by institutional review boards, or IRBs). In some embodiments, a high risk clinical trial is a drug trial. As used herein, the term “low risk clinical trial” refers to one in which the test agent has “minimal risk” (as defined by the terminology used by IRBs). In some embodiments, a low risk clinical trial is one that is not a drug trial. In some embodiments, a low risk clinical trial is one DB1 / 147901903.2 58 that that involves the use of a monitor or clinical practice process. In some embodiments, a low risk clinical trial is an observational clinical trial. As used herein, the terms “modulated” or “modulation,” or “regulated” or “regulation” and “differentially regulated” can refer to both up regulation (i.e., activation or stimulation, e.g., by agonizing or potentiating) and down regulation (i.e., inhibition or suppression, e.g., by antagonizing, decreasing or inhibiting), unless otherwise specified or clear from the context of a specific usage. As used herein, the term “subject” refers to any suitable (e.g., treatable) member of the animal kingdom. In the methods, the subject is preferably a mammal. In the methods, the subject is preferably a human patient. In the methods, the subject may be a mammalian pediatric patient. In the methods, the pediatric patient is a mammalian (e.g., preferably human) patient under 18 years of age, while an adult patient is 18 or older. As used herein, the term “treating” (and its variations, such as “treatment” “treating,” “treat,” and the like) is, unless stated otherwise, to be considered in its broadest context and refers to obtaining a desired pharmacologic and / or physiologic effect. In particular, for example, the term “treating” may not necessarily imply or require that an animal is treated until total recovery. Accordingly, “treating” includes amelioration of the symptoms, relief from the symptoms or effects associated with a condition, decrease in severity of a condition, or preventing, preventively ameliorating symptoms, or otherwise reducing the risk of developing a particular condition. In some aspects, “treating” may not require or include prevention. As used herein, reference to “treating” an animal includes but is not limited to prophylactic treatment and therapeutic treatment. The effect can be prophylactic in terms of completely or partially preventing a disease or symptom thereof and / or can be therapeutic in terms of a partial or complete cure for a disease and / or adverse effect attributable to the disease. “Treatment,” as used herein, covers any treatment of a disease in a subject, preferably in a mammal (e.g., in a human), and may include one or more of: (a) preventing the disease from occurring in a subject which may be predisposed to the disease but has not yet been diagnosed as having it; (b) inhibiting the disease, i.e., arresting its development; and (c) relieving the disease, i.e., causing regression or elimination of the disease and / or relieving one or more disease symptoms. In particular aspects of the methods, such as conditions or disorders characterized by dysregulated IRAK expression or dysregulated (e.g., hyperactive) IRAK-mediated signaling pathway(s), treatment may be or DB1 / 147901903.2 59 include reducing such expression or signaling. “Treatment” can also encompass delivery of an agent or administration of a therapy in order to provide for a pharmacologic effect, even in the absence of a disease or condition. Any of the compositions (e.g., pharmaceutical compositions) described herein can be used to treat a suitable subject. “Therapeutically effective amount” means an amount effective to achieve a desired and / or beneficial effect. An effective amount can be administered in one or more administrations. In the methods, a therapeutically effective amount is an amount appropriate to treat an indication. By treating an indication is meant achieving any desirable effect, such as one or more of palliate, ameliorate, stabilize, reverse, slow, or delay disease progression, increase the quality of life, or to prolong life. Such achievement can be measured by any suitable method, such as measurement of tumor size or blood cell count, or any other suitable measurement. As used herein, the term “marker” or “biomarker” refers to a biological molecule, such as, for example, a nucleic acid, peptide, protein, hormone, and the like, whose presence or concentration can be detected and correlated with a known condition, such as a disease state. It can also be used to refer to a differentially expressed gene whose expression pattern can be utilized as part of a predictive, prognostic or diagnostic process in healthy conditions or a disease state, or which, alternatively, can be used in methods for identifying a useful treatment or prevention therapy. As used herein, an mRNA “isoform” is an alternative transcript for a specific mRNA or gene. This term includes pre-mRNA, immature mRNA, mature mRNA, cleaved or otherwise truncated, shortened, or aberrant mRNA, modified mRNA (e.g. containing any residue modifications, capping variants, polyadenylation variants, etc.), and the like. “Antibody” or “antibody peptide(s)” refer to an intact antibody, or a binding fragment thereof that competes with the intact antibody for specific binding; this definition also encompasses monoclonal and polyclonal antibodies. Binding fragments are produced by recombinant DNA techniques, or by enzymatic or chemical cleavage of intact antibodies. Binding fragments include Fab, Fab′, F(ab′)2, Fv, and single-chain antibodies. An antibody other than a “bispecific” or “bifunctional” antibody is understood to have each of its binding sites identical. An antibody, for example, substantially inhibits adhesion of a receptor to a counterreceptor when an excess of antibody reduces the quantity of receptor bound to DB1 / 147901903.2 60 counterreceptor by at least about 20%, 40%, 60% or 80%, and more usually greater than about 85% (as measured in an in vitro competitive binding assay). Embodiments of the disclosure set forth herein include disclosed compounds (e.g., Compound 8). Other embodiments include compositions (e.g., pharmaceutical compositions) comprising the disclosed compound. Still other embodiments of the disclosure include compositions (e.g., pharmaceutical compositions) for treating, for example, certain diseases using the disclosed compounds. Some embodiments include methods of using the disclosed compound (e.g., in compositions or in pharmaceutical compositions) for administering and treating (e.g., diseases such as cancer or blood disorders). Some embodiments include methods of determining whether a patient is suitable for, or likely to respond favorably to, a particular treatment. Further embodiments include methods for making the disclosed compounds. Additional embodiments of the disclosure are also discussed herein. Compounds In one aspect, the present disclosure relates to or a salt, ester, solvate, optical isomer, geometric isomer, or embodiment, the compounds disclosed herein (i.e., Compound 8 or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof) are an IRAK1, IRAK4, IRAK1 / 4, and / or FLT3 inhibitor. In one embodiment, the compounds disclosed herein are IRAK1 / 4, panFLT3 inhibitors. In one embodiment, Compound 8 or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof has an IRAK1 IC50 of less than about 55 nM, less than about 50 nM, less than about 45 nM, less than about 40 nM, less than about 35 nM, less than about 30 nM, less than about 25 nM, less than about 20 nM, less than about 15 nM, less than about 10 nM, or less than about 5 nM. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof has an IRAK1 IC50 of between about 27 nM and about 17 nM. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, DB1 / 147901903.2 61 geometric isomer, or salt of an isomer thereof has an IRAK1 IC50 of about 30 nM, about 29 nM, about 28 nM, about 27 nM, about 25 nM, about 24 nM, about 23 nM, about 22 nM, about 21 nM, about 20 nM, about 19 nM, about 18 nM, about 17 nM, about 16 nM, or about 15 nM. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof has an IRAK4 IC50 of less than about 30 nM, less than about 25 nM, less than about 20 nM, less than about 15 nM, less than about 10 nM, or less than about 5 nM. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof has an IRAK4 IC50 of between about 5 nM and about 0.05 nM. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof has an IRAK4 IC50of about 5 nM, about 4.5 nM, about 4 nM, about 3.5 nM, about 3 nM, about 2.5 nM, about 2 nM, about 1.5 nM, about 1 nM, or about 0.5 nM. In one embodiment, the compound has IRAK4:IRAK1 potency ratio of less than about 70, less than about 60, less than about 50, less than about 40, less than about 30, or less than about 20. In one embodiment, the IRAK4:IRAK1 potency ratio is calculated from the IRAK1 and IRAK4 IC50 measurements. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof has a FLT3 IC50of less than about 10 nM, less than about 8 nM, less than about 6 nM, less than about 4 nM, less than about 2 nM, or less than about 1 nM. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof has a FLT3 IC50of between about 2 nM and about 0.01 nM. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof has a FLT3 IC50 of about 2.5 nM, about 2.25 nM, about 2 nM, about 1.75 nM, about 1.5 nM, about 1.25 nM, about 1 nM, about 0.75 nM, about 0.5 nM, about 0.25 nM, about 0.1 nM, or about 0.075 nM. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, inhibits NF-kB-mediated signaling. In one embodiment, inhibition of IRAK1 and IRAK4 inhibits NF-kB-mediated signaling. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, inhibits TLR signaling and IL-1 signaling. In one embodiment, the inhibition of IRAK1 and IRAK4 inhibits TLR signaling and IL-1 signaling. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, inhibits IRAK1, IRAK4, and FLT3 DB1 / 147901903.2 62 Methods In one aspect, the present disclosure provides a method of treating an inflammatory disease / disorder, acute myeloid leukemia (AML), or myelodysplastic syndrome (MDS) in a subject in need thereof, the method comprising administering to the subject Compound 8: or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof. In one embodiment, the inflammatory disease / disorder is selected from chronic inflammation, sepsis, rheumatoid arthritis, hidradenitis suppurativa, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, psoriasis, Sjögren’s syndrome, Ankylosing spondylitis, systemic sclerosis, Type 1 diabetes mellitus, Crohn’s disease, atopic dermatitis, and colitis. In one embodiment, the subject has or is suspected of having AML. In one embodiment, the AML is relapsed AML, refractory AML, relapsed / refractory AML, AML with resistance to hypomethylating agents, AML with resistance to venetoclax, AML with resistance to hypomethylating agents and venetoclax, monocytic AML, or monocytic-like AML. In one embodiment, the AML is FLT3 wild type AML. In another embodiment, the AML is FLT3 mutant AML. In one embodiment, the subject has or is suspected of having MDS. In one embodiment, the MDS is MDS with a splicing factor mutation, MDS with a mutation in isocitrate dehydrogenase 1, or MDS with a mutation in isocitrate dehydrogenase 2. In one embodiment, the MDS with a splicing factor mutation comprises MDS with a splicing factor mutation in U2AF1, SRSF2, SF3B1, or ZRSR2. In one embodiment, the subject has FLT3 wild type AML. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in one or more of TET2, KIT, BCOR, BRAF, CDKN2A, UTX, ZRSR2, NPM1, PTEN, DNMT3A, EZH2, RUNX1, JAK2, ASXL1, ABL1, BCORL1, FBXW7, KDM6A, KRAS, SRSF2, TP53, CALR, ATRX, IDH1, IDH2, PDGFRA, SF3B1, GATA1, PTPN11, HRAS, MPL, PHF6, ATM, BCL11A, MLL3, TYK1, DB1 / 147901903.2 63 UTAF1, CTCF, CEBPA, ETV6, NOTCH1, STAG2, SETBP1, or WT1. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in one or more of TET2, KIT, or BCOR. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in each of TET2, KIT, and BCOR. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in one or more of TET2, BRAF, CDKN2A, or UTX. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in each of TET2, BRAF, CDKN2A, and UTX. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in one or more of ZRSR2, TET2, NPM1, PTEN, DNMT3A, or EZH2. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in each of ZRSR2, TET2, NPM1, PTEN, DNMT3A, and EZH2. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in one or more of TET2, RUNX1, JAK2, DNMT3A, or ASXL1. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in each of TET2, RUNX1, JAK2, DNMT3A, and ASXL1. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in one or more of ABL1, ASXL1, BCORL1, CBL, CDKN2A, FBXW7, KDM6A, KIT, KRAS, PTEN, SRSF2, TET2, or TP53. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in each of ABL1, ASXL1, BCORL1, CBL, CDKN2A, FBXW7, KDM6A, KIT, KRAS, PTEN, SRSF2, TET2, and TP53. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in one or more of ABL1, ASXL1, ATRX, BCOR, BCORL1, CALR, CDKN2A, DNMT3A, IDH1, KIT, KRAS, PDGFRA, PTEN, SF3B1, TET2, or TP53. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in each of ABL1, ASXL1, ATRX, BCOR, BCORL1, CALR, CDKN2A, DNMT3A, IDH1, KIT, KRAS, PDGFRA, PTEN, SF3B1, TET2, and TP53. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in one or more of ASXL1, BCORL1, BRAF, CDKN2A, DNMT3A, EZH2, HRAS, KIT, KRAS, MPL, PHF6, PTEN, RUNX1, TET2, TP53, or WT1. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in each of ASXL1, BCORL1, BRAF, CDKN2A, DNMT3A, EZH2, HRAS, KIT, KRAS, MPL, PHF6, PTEN, RUNX1, TET2, TP53, and WT1. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in one or more of ABL1, ASXL1, ATRX, BCORL1, CBL, CDKN2A, DNMT3A, GATA1, JAK2, KDM6A, KIT, KRAS, PTEN, PTPN11, SRSF2, TET2, or TP53. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in each of ABL1, ASXL1, ATRX, BCORL1, CBL, CDKN2A, DNMT3A, GATA1, JAK2, KDM6A, KIT, KRAS, DB1 / 147901903.2 64 PTEN, PTPN11, SRSF2, TET2, and TP53. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in one or more of BCL11A, RUNX1, ATM, DNMT3A, CTCF, KIT, U2AF1, IDH1, TYK2, or MLL3. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in each of BCL11A, RUNX1, ATM, DNMT3A, CTCF, KIT, U2AF1, IDH1, TYK2, and MLL3. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in one or more of ABL1, ASXL1, BCORL1, BRAF, CDKN2A, CEBPA, DNMT3A, ETV6, EZH2, IDH2, KDM6A, KIT, KRAS, PTEN, RUNX1, SF3B1, TET2, TP53, or ZRSR2. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in each of ABL1, ASXL1, BCORL1, BRAF, CDKN2A, CEBPA, DNMT3A, ETV6, EZH2, IDH2, KDM6A, KIT, KRAS, PTEN, RUNX1, SF3B1, TET2, TP53, and ZRSR2. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in one or more of ASXL1, ATRX, BCORL1, BRAF, DNMT3A, EZH2, FBXW7, GATA1, KDM6A, KIT, KRAS, NOTCH1, PTEN, RUNX1, STAG2, TET2, or TP53. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in each of ASXL1, ATRX, BCORL1, BRAF, DNMT3A, EZH2, FBXW7, GATA1, KDM6A, KIT, KRAS, NOTCH1, PTEN, RUNX1, STAG2, TET2, and TP53. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in one or more of ABL1, ASXL1, BCORL1, CDKN2A, CEBPA, HRAS, IDH1, KDM6A, KRAS, NOTCH1, PTEN, SRSF2, or TP53. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in each of ABL1, ASXL1, BCORL1, CDKN2A, CEBPA, HRAS, IDH1, KDM6A, KRAS, NOTCH1, PTEN, SRSF2, and TP53. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in one or more of ATRX, BCOR, BCORL1, BRAF, CDKN2A, FBXW7, KIT, NRAS, PTEN, RUNX1, STAG2, TET2, or TP53. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in each of ATRX, BCOR, BCORL1, BRAF, CDKN2A, FBXW7, KIT, NRAS, PTEN, RUNX1, STAG2, TET2, and TP53. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in one or more of ABL1, ASXL1, BCOR, BCORL1, BRAF, CDKN2A, ETV6, FBXW7, KDM6A, KRAS, PTEN, PTPN11, RUNX1, SETBP1, SRSF2, TET2, TP53, or WT1. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in each of ABL1, ASXL1, BCOR, BCORL1, BRAF, CDKN2A, ETV6, FBXW7, KDM6A, KRAS, PTEN, PTPN11, RUNX1, SETBP1, SRSF2, TET2, TP53, and WT1. In one embodiment, Compound 8, or a salt, ester, solvate, optical DB1 / 147901903.2 65 isomer, geometric isomer, or salt of an isomer thereof treats FLT3 wild type AML regardless of the additional AML mutational status of the subject. In one embodiment, the subject has FLT3 mutant AML with a FLT3-ITD mutation and a gene mutation in one or more of TET2, DNMT3A, or NPM1. In one embodiment, the subject has FLT3 mutant AML with a FLT3-ITD mutation and a gene mutation in each of TET2, DNMT3A, and NPM1. In one embodiment, the subject has FLT3 mutant AML with a FLT3- ITD mutation and / or a FLT3(D835Y) mutation. In one embodiment, the subject has FLT3 mutant AML with each of a FLT3-ITD mutation and a FLT3(D835Y) mutation. In one embodiment, the subject has FLT3 mutant AML with a gene mutation in FLT3 and in one or more of ABL1, ATRX, BCORL1, BRAF, CDKN2A, DNMT3A, KDM6A, KRAS, PTEN, PTPN11, RUNX1, TET2, or TP53. In one embodiment, the subject has FLT3 mutant AML with a gene mutation in FLT3 and in each of ABL1, ATRX, BCORL1, BRAF, CDKN2A, DNMT3A, KDM6A, KRAS, PTEN, PTPN11, RUNX1, TET2, and TP53. In one embodiment, the subject has FLT3 mutant AML with a gene mutation in FLT3 and in one or more of ASXL1, BCORL1, CDKN2A, CEBPA, DNMT3A, FBXW7, HRAS, IDH1, JAK2, KIT, NPM1, NRAS, PDGFRA, PTEN, PTPN11, SF3B1, TET2, or TP53. In one embodiment, the subject has FLT3 mutant AML with a gene mutation in FLT3 and in each of ASXL1, BCORL1, CDKN2A, CEBPA, DNMT3A, FBXW7, HRAS, IDH1, JAK2, KIT, NPM1, NRAS, PDGFRA, PTEN, PTPN11, SF3B1, TET2, and TP53. In one embodiment, the subject has FLT3 mutant AML with a gene mutation in FLT3 and in one or more of ASXL1, BCORL1, BRAF, CBL, DNMT3A, ETV6, JAK2, KIT, PDGFRA, PHF6, PTEN, PTPN11, RUNX1, TET2, or TP53. In one embodiment, the subject has FLT3 mutant AML with a gene mutation in FLT3 and in each of ASXL1, BCORL1, BRAF, CBL, DNMT3A, ETV6, JAK2, KIT, PDGFRA, PHF6, PTEN, PTPN11, RUNX1, TET2, and TP53. In one embodiment, the subject has FLT3 mutant AML with a gene mutation in FLT3 and in one or more of ABL1, ASXL1, ATRX, BCORL1, CDKN2A, CEBPA, FBXW7, GATA1, KRAS, NOTCH1, PTEN, TET2, TP53, or WT1. In one embodiment, the subject has FLT3 mutant AML with a gene mutation in FLT3 and in each of ABL1, ASXL1, ATRX, BCORL1, CDKN2A, CEBPA, FBXW7, GATA1, KRAS, NOTCH1, PTEN, TET2, TP53, and WT1. In one embodiment, the subject has FLT3 mutant AML with a gene mutation in FLT3 and in one or more of ABL1, ASXL1, ATRX, BCORL1, CDKN2A,DNMT3A, ETV6, KDM6A, KIT, KRAS, NOTCH1, NRAS, PDGFRA, PTEN, PTPN11, RUNX1, SETBP1, TET2, DB1 / 147901903.2 66 or TP53. In one embodiment, the subject has FLT3 mutant AML with a gene mutation in FLT3 and in each of ABL1, ASXL1, ATRX, BCORL1, CDKN2A,DNMT3A, ETV6, KDM6A, KIT, KRAS, NOTCH1, NRAS, PDGFRA, PTEN, PTPN11, RUNX1, SETBP1, TET2, and TP53. In one embodiment, the subject has FLT3 mutant AML with a gene mutation in FLT3 and in one or more of ABL1, ASXL1, ATRX, BCORL1, BRAF, CBL, CDKN2A, ETV6, GNAS, HRAS, JAK2, KDM6A, PTEN, TET2, or TP53. In one embodiment, the subject has FLT3 mutant AML with a gene mutation in FLT3 and in each of ABL1, ASXL1, ATRX, BCORL1, BRAF, CBL, CDKN2A, ETV6, GNAS, HRAS, JAK2, KDM6A, PTEN, TET2, and TP53. In one embodiment, the subject has FLT3 mutant AML with a gene mutation in FLT3 and in one or more of ABL1, ASXL1, BCORL1, BRAF, CBL, CDKN2A, FBX, HRAS, IDH2, KDM6A, KIT, PTEN, RAD21, RUI, TET2, or TP53. In one embodiment, the subject has FLT3 mutant AML with a gene mutation in FLT3 and in each of ABL1, ASXL1, BCORL1, BRAF, CBL, CDKN2A, FBX, HRAS, IDH2, KDM6A, KIT, PTEN, RAD21, RUI, TET2, and TP53. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof treats FLT3 mutant AML regardless of the additional AML mutational status of the subject. In one embodiment, the subject has MDS with a gene mutation in U2AF1. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof treats MDS regardless of the MDS mutational status of the subject. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof has an IRAK1 IC50 of less than about 55 nM, less than about 50 nM, less than about 45 nM, less than about 40 nM, less than about 35 nM, less than about 30 nM, less than about 25 nM, less than about 20 nM, less than about 15 nM, less than about 10 nM, or less than about 5 nM. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof has an IRAK1 IC50 of between about 27 nM and about 17 nM. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof has an IRAK1 IC50 of about 30 nM, about 29 nM, about 28 nM, about 27 nM, about 25 nM, about 24 nM, about 23 nM, about 22 nM, about 21 nM, about 20 nM, about 19 nM, about 18 nM, about 17 nM, about 16 nM, or about 15 nM. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof has an IRAK4 IC50 of less than about 30 nM, less than about 25 nM, less DB1 / 147901903.2 67 than about 20 nM, less than about 15 nM, less than about 10 nM, or less than about 5 nM. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof has an IRAK4 IC50of between about 5 nM and about 0.05 nM. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof has an IRAK4 IC50 of about 5 nM, about 4.5 nM, about 4 nM, about 3.5 nM, about 3 nM, about 2.5 nM, about 2 nM, about 1.5 nM, about 1 nM, or about 0.5 nM. In one embodiment, the compound has IRAK4:IRAK1 potency ratio of less than about 70, less than about 60, less than about 50, less than about 40, less than about 30, or less than about 20. In one embodiment, the IRAK4:IRAK1 potency ratio is calculated from the IRAK1 and IRAK4 IC50measurements. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof has a FLT3 IC50 of less than about 10 nM, less than about 8 nM, less than about 6 nM, less than about 4 nM, less than about 2 nM, or less than about 1 nM. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof has a FLT3 IC50 of between about 2 nM and about 0.01 nM. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof has a FLT3 IC50of about 2.5 nM, about 2.25 nM, about 2 nM, about 1.75 nM, about 1.5 nM, about 1.25 nM, about 1 nM, about 0.75 nM, about 0.5 nM, about 0.25 nM, about 0.1 nM, or about 0.075 nM. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, inhibits NF-kB-mediated signaling. In one embodiment, inhibition of IRAK1 and IRAK4 inhibits NF-kB-mediated signaling. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof inhibits TLR signaling and IL-1 signaling. In one embodiment, the inhibition of IRAK1 and IRAK4 inhibits TLR signaling and IL-1 signaling. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, inhibits IRAK1, IRAK4, and FLT3. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof inhibits FLT3. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, treats AML and / or MDS in the subject by suppressing leukemic stem / progenitor cell (LSPC) function and inducing differentiation. In one embodiment, the inhibition of IRAK1 and DB1 / 147901903.2 68 IRAK4 by the compound of the disclosure promotes the suppression of LSPC function and the induction of differentiation in the subject with AML and / or MDS. In one embodiment, the subject in need thereof has elevated expression of one or more IRAK1 / 4-associated genes and / or decreased expression of one or more IRAK1 / 4-associated genes. In one embodiment, the subject in need thereof has elevated expression of one or more IRAK1 / 4-associated genes compared to a healthy control subject and / or decreased expression of one or more IRAK1 / 4-associated genes compared to a healthy control subject. In one embodiment, the subject in need thereof has elevated expression of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 IRAK1 / 4-associated genes. In one embodiment, the subject in need thereof has elevated expression of one or more IRAK1 / 4- associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3. In one embodiment, the subject in need thereof has elevated expression of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3. In one embodiment, the subject in need thereof has decreased expression of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 IRAK1 / 4-associated genes compared to a DB1 / 147901903.2 69 healthy control subject. In one embodiment, the subject in need thereof has decreased expression of one or more IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3. In one embodiment, the subject in need thereof has decreased expression of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3. In one embodiment, the subject in need thereof has increased secretion of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, or thirteen cytokines. In one embodiment, the subject in need thereof has increased secretion of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, or thirteen cytokines selected from: TNF-α, IL-1 β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, IL-23, GM-CSF, and IFN-γ. In one embodiment, the subject in need thereof has increased secretion of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, or thirteen cytokines compared to a healthy control subject. In one embodiment, the subject in need thereof has increased secretion of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, or thirteen cytokines selected from: TNF-α, IL-1 β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, IL-23, GM-CSF, and IFN-γ compared to the healthy control subject. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, decreases the expression of one of more IRAK1 / 4-associated genes found to be elevated in the subject and / or increases the expression of one of more DB1 / 147901903.2 70 IRAK1 / 4-associated genes found to be decreased in the subject. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, decreases the expression of one of more IRAK1 / 4-associated genes found to be elevated in the subject before the administration of Compound 8 and / or increases the expression of one of more IRAK1 / 4-associated genes found to be decreased in the subject before the administration of Compound 8. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, decreases the expression of one of more IRAK1 / 4-associated genes found to be elevated in the subject compared to a healthy control subject and / or increases the expression of one of more IRAK1 / 4-associated genes found to be decreased in the subject compared to a healthy control subject. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, decreases the expression of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 IRAK1 / 4-associated genes in the subject in need thereof. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, decreases the expression of one or more IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3 in the subject in need thereof. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, decreases the expression of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, DB1 / 147901903.2 71 PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3 in the subject in need thereof. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, increases the expression of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 IRAK1 / 4-associated genes in the subject in need thereof. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, increases the expression of one or more IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3 in the subject in need thereof. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, increases the expression of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3 in the subject in need thereof. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof decreases the secretion of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, or thirteen cytokines in the subject in need thereof. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an DB1 / 147901903.2 72 isomer thereof decreases the secretion of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, or thirteen cytokines selected from: TNF-α, IL-1 β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, IL-23, GM-CSF, and IFN-γ in the subject in need thereof. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, is administered to the subject in need thereof via parenteral administration, mucosal administration, intravenous administration, subcutaneous administration, topical administration, intradermal administration, oral administration, sublingual administration, intranasal administration, or intramuscular administration. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, is administered to the subject in need thereof in an amount of from about 0.005 mg / kg subject body weight to about 1,000 mg / kg subject body weight. In one embodiment, a composition comprising Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, is administered to the subject in need thereof. In one embodiment, the composition comprising Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof further comprises one or more pharmaceutically acceptable carriers, excipients, or additives. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, is more effective at inhibiting cancer cell colony formation and / or cancer progenitor cell function when compared to a compound which inhibits IRAK1 without inhibiting IRAK4 or inhibits IRAK4 without inhibiting IRAK1. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, provides sustained treatment of the inflammatory disease / disorder, AML, or MDS in the subject. In one embodiment, the sustained treatment is greater than the treatment provided from a compound which inhibits IRAK1 without inhibiting IRAK4 or inhibits IRAK4 without inhibiting IRAK1. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, continues to treat the inflammatory disease / disorder, AML, or MDS in the subject after the administration is stopped. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, continues to treat the inflammatory disease / disorder, AML, or MDS in the subject for about 1 day, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, DB1 / 147901903.2 73 about one week, about two weeks, about three weeks, or about a month after the administration is stopped. In one embodiment, the method further comprises administering Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, in combination with one or more additional agents selected from: a chemotherapy agent, a BCL2 inhibitor, an immune modulator, a BTK inhibitor, a DNA methyltransferase inhibitor / hypomethylating agent, an anthracycline, a histone deacetylase (HDAC) inhibitor, a purine nucleoside analogue (antimetabolite), an isocitrate dehydrogenase 1 or 2 (IDH1 and / or IDH2) inhibitor, an antibody- drug conjugate, an mAbs / immunotherapy, a Plk inhibitor, a MEK inhibitor, a CDK inhibitor, a CDK9 inhibitor, a CDK8 inhibitor, a retinoic acid receptor agonist, a TP53 activator, a CELMoD, a smoothened receptor antagonist, an ERK inhibitor including an ERK2 / MAPK1 or ERK1 / MAPK3 inhibitor, a PI3K inhibitor, an mTOR inhibitor, a steroid or glucocorticoid, a steroid or glucocorticoid receptor modulator, an EZH2 inhibitor, a hedgehog (Hh) inhibitor, a Topoisomerase I inhibitor, a Topoisomerase II inhibitor, an aminopeptidase / Leukotriene A4 hydrolase inhibitor, a FLT3 / Axl / ALK inhibitor, a FLT3 / KIT / PDGFR, PKC, and / or KDR inhibitor, a Syk inhibitor, an E-selectin inhibitor, an NEDD8-activator, an MDM2 inhibitor, a PLK1 inhibitor, an Aura A inhibitor, an aurora kinase inhibitor, an EGFR inhibitor, an AuroraB / C / VEGFR1 / 2 / 3 / FLT3 / CSF-1R / Kit / PDGFRA / B inhibitor, an AKT 1, 2, and / or 3 inhibitor, a ABL1 / 2 / SRC / EPHA2 / LCK / YES1 / KIT / PDGFRB / FYN inhibitor, a farnesyltransferase inhibitor, a BRAF / MAP2K1 / MAP2K2 inhibitor, a Menin-KMT2A / MLL inhibitor, and a multikinase inhibitor. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, is administered to the subject in need thereof in combination with at least one of a BCL2 inhibitor, a BTK inhibitor, a gluococorticoid, a CDK inhibitor, and a DNA methyltransferase inhibitor. In one embodiment, the BCL2 inhibitor is venetoclax or a pharmaceutically acceptable salt thereof. In one embodiment, the BTK inhibitor is ibrutinib or a pharmaceutically acceptable salt thereof. In one embodiment, the glucocorticoid is selected from dexamethasone, methylprednisolone, prednisolone or a pharmaceutically acceptable salt of any one thereof. In one embodiment, the CDK inhibitor is a CDK4 inhibitor, a CDK6 inhibitor, a CDK7 inhibitor, and / or a CDK9 inhibitor. In one embodiment, the CDK inhibitor is selected from CDK4 / 6 inhibitor Palbociclib, CDK7 inhibitor THZ1, and / or CDK9 inhibitors BAY1251152 and Atuveciclib, or a DB1 / 147901903.2 74 pharmaceutically acceptable salt of any one thereof. In one embodiment, the DNA methyltransferase inhibitor is azacitidine or a pharmaceutically acceptable salt thereof. In one embodiment, one or more compositions comprising the one or more additional agents are administered to the subject in need thereof. In one embodiment, the one or more compositions comprising the one or more additional agents further comprise a pharmaceutically acceptable carrier, excipient, or additive. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, is administered sequentially with the one or more additional agents. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, is administered concurrently with the one or more additional agents. In one embodiment, the composition comprising Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, is administered sequentially with the composition comprising the one or more additional agents. one embodiment, the composition comprising Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, is administered concurrently with the composition comprising the one or more additional agents. In another aspect, the present disclosure provides a method of determining a subject with a disease / disorder that can be treated by the administration of Compound 8 or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, the method comprising: determining that a subject with an inflammatory disease / disorder, acute myeloid leukemia (AML), or myelodysplastic syndrome (MDS) has elevated expression of one or more IRAK1 / 4- associated genes and / or decreased expression of one or more IRAK1 / 4-associated genes; and administering to the subject Compound 8: or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, thus treating the inflammatory disease / disorder, AML, or MDS. In one embodiment, the subject in need thereof has elevated expression of one or more IRAK1 / 4-associated genes and / or decreased DB1 / 147901903.2 75 expression of one or more IRAK1 / 4-associated genes compared to a healthy control subject. In one embodiment, the inflammatory disease / disorder is selected from chronic inflammation, sepsis, rheumatoid arthritis, hidradenitis suppurativa, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, psoriasis, Sjögren’s syndrome, Ankylosing spondylitis, systemic sclerosis, Type 1 diabetes mellitus, Crohn’s disease, atopic dermatitis, and colitis. In one embodiment, the subject has or is suspected of having AML. In one embodiment, the AML is relapsed AML, refractory AML, relapsed / refractory AML, AML with resistance to hypomethylating agents, AML with resistance to venetoclax, AML with resistance to hypomethylating agents and venetoclax, monocytic AML, or monocytic-like AML. In one embodiment, the AML is FLT3 wild type AML. In another embodiment, the AML is FLT3 mutant AML. In one embodiment, the subject has or is suspected of having MDS. In one embodiment, the MDS is MDS with a splicing factor mutation, MDS with a mutation in isocitrate dehydrogenase 1, or MDS with a mutation in isocitrate dehydrogenase 2. In one embodiment, the MDS with a splicing factor mutation comprises MDS with a splicing factor mutation in U2AF1, SRSF2, SF3B1, or ZRSR2. In one embodiment, the subject has FLT3 wild type AML. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in one or more of TET2, KIT, BCOR, BRAF, CDKN2A, UTX, ZRSR2, NPM1, PTEN, DNMT3A, EZH2, RUNX1, JAK2, or ASXL1. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in one or more of TET2, KIT, or BCOR. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in each of TET2, KIT, and BCOR. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in one or more of TET2, BRAF, CDKN2A, or UTX. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in each of TET2, BRAF, CDKN2A, and UTX. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in one or more of ZRSR2, TET2, NPM1, PTEN, DNMT3A, or EZH2. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in each of ZRSR2, TET2, NPM1, PTEN, DNMT3A, and EZH2. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in one or more of TET2, RUNX1, JAK2, DNMT3A, or ASXL1. In one embodiment, the subject has FLT3 wild type AML with a gene mutation in each of TET2, RUNX1, JAK2, DNMT3A, and ASXL1. In one embodiment, Compound 8, or a salt, ester, DB1 / 147901903.2 76 solvate, optical isomer, geometric isomer, or salt of an isomer thereof treats FLT3 wild type AML regardless of the additional AML mutational status of the subject. In one embodiment, the subject has FLT3 mutant AML with a FLT3-ITD mutation and a gene mutation in one or more of TET2, DNMT3A, or NPM1. In one embodiment, the subject has FLT3 mutant AML with a FLT3-ITD mutation and a gene mutation in each of TET2, DNMT3A, and NPM1. In one embodiment, the subject has FLT3 mutant AML with a FLT3- ITD mutation and / or a FLT3(D835Y) mutation. In one embodiment, the subject has FLT3 mutant AML with each of a FLT3-ITD mutation and a FLT3(D835Y) mutation. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof treats FLT3 mutant AML regardless of the additional AML mutational status of the subject. In one embodiment, the subject has MDS with a gene mutation in U2AF1. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof treats MDS regardless of the MDS mutational status of the subject. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof has an IRAK1 IC50of less than about 55 nM, less than about 50 nM, less than about 45 nM, less than about 40 nM, less than about 35 nM, less than about 30 nM, less than about 25 nM, less than about 20 nM, less than about 15 nM, less than about 10 nM, or less than about 5 nM. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof has an IRAK1 IC50of between about 27 nM and about 17 nM. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof has an IRAK1 IC50of about 30 nM, about 29 nM, about 28 nM, about 27 nM, about 25 nM, about 24 nM, about 23 nM, about 22 nM, about 21 nM, about 20 nM, about 19 nM, about 18 nM, about 17 nM, about 16 nM, or about 15 nM. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof has an IRAK4 IC50of less than about 30 nM, less than about 25 nM, less than about 20 nM, less than about 15 nM, less than about 10 nM, or less than about 5 nM. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof has an IRAK4 IC50of between about 5 nM and about 0.05 nM. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof has an IRAK4 IC50 of about 5 nM, about 4.5 nM, about 4 nM, about 3.5 nM, DB1 / 147901903.2 77 about 3 nM, about 2.5 nM, about 2 nM, about 1.5 nM, about 1 nM, or about 0.5 nM. In one embodiment, the compound has IRAK4:IRAK1 potency ratio of less than about 70, less than about 60, less than about 50, less than about 40, less than about 30, or less than about 20. In one embodiment, the IRAK4:IRAK1 potency ratio is calculated from the IRAK1 and IRAK4 IC50 measurements. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof has a FLT3 IC50of less than about 10 nM, less than about 8 nM, less than about 6 nM, less than about 4 nM, less than about 2 nM, or less than about 1 nM. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof has a FLT3 IC50of between about 2 nM and about 0.01 nM. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof has a FLT3 IC50 of about 2.5 nM, about 2.25 nM, about 2 nM, about 1.75 nM, about 1.5 nM, about 1.25 nM, about 1 nM, about 0.75 nM, about 0.5 nM, about 0.25 nM, about 0.1 nM, or about 0.075 nM. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, inhibits NF-kB-mediated signaling. In one embodiment, inhibition of IRAK1 and IRAK4 inhibits NF-kB-mediated signaling. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof inhibits TLR signaling and IL-1 signaling. In one embodiment, the inhibition of IRAK1 and IRAK4 inhibits TLR signaling and IL-1 signaling. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, inhibits IRAK1, IRAK4, and FLT3. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof inhibits FLT3. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, treats AML and / or MDS in the subject by suppressing leukemic stem / progenitor cell (LSPC) function and inducing differentiation. In one embodiment, the inhibition of IRAK1 and IRAK4 by the compound of the disclosure promotes the suppression of LSPC function and the induction of differentiation in the subject with AML and / or MDS. In one embodiment, the subject in need thereof has elevated expression of one or more IRAK1 / 4-associated genes and / or decreased expression of one or more IRAK1 / 4-associated genes. In one embodiment, the subject in need thereof has elevated expression of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, DB1 / 147901903.2 78 seventeen, eighteen, nineteen, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 IRAK1 / 4-associated genes. In one embodiment, the subject in need thereof has elevated expression of one or more IRAK1 / 4- associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3. In one embodiment, the subject in need thereof has elevated expression of one or more IRAK1 / 4-associated genes compared to a healthy control subject and / or decreased expression of one or more IRAK1 / 4- associated genes compared to a healthy control subject. In one embodiment, the subject in need thereof has elevated expression of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 IRAK1 / 4-associated genes compared to a healthy control subject. In one embodiment, the subject in need thereof has elevated expression of one or more IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3 compared to the healthy control subject. In one embodiment, the subject in need thereof has elevated expression of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, DB1 / 147901903.2 79 CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3 compared to the healthy control subject. In one embodiment, the subject in need thereof has decreased expression of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 IRAK1 / 4-associated genes. In one embodiment, the subject in need thereof has decreased expression of one or more IRAK1 / 4- associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3. In one embodiment, the subject in need thereof has decreased expression of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3. In one embodiment, the subject in need thereof has decreased expression of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 IRAK1 / 4-associated genes compared to a healthy control subject. In one embodiment, the subject in need thereof has decreased expression of one or more IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, DB1 / 147901903.2 80 SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3 compared to the healthy control subject. In one embodiment, the subject in need thereof has decreased expression of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3 compared to the healthy control subject. In one embodiment, the subject in need thereof has elevated secretion of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, or thirteen cytokines. In one embodiment, the subject in need thereof has elevated secretion of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, or thirteen cytokines selected from: TNF-α, IL-1 β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, IL-23, GM-CSF, and IFN-γ. In one embodiment, the subject in need thereof has elevated secretion of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, or thirteen cytokines compared to a healthy control subject. In one embodiment, the subject in need thereof has elevated secretion of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, or thirteen cytokines selected from: TNF-α, IL-1 β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, IL-23, GM-CSF, and IFN-γ compared to the healthy control subject. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, decreases the expression of one of more IRAK1 / 4-associated genes found to be elevated in the subject before the administration of Compound 8 and / or increases the expression of one of more IRAK1 / 4-associated genes found to be decreased in the subject before the administration of Compound 8. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, decreases the DB1 / 147901903.2 81 expression of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 IRAK1 / 4-associated genes in the subject in need thereof. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, decreases the expression of one or more IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3 in the subject in need thereof. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, decreases the expression of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3 in the subject in need thereof. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, decreases the expression of one of more IRAK1 / 4-associated genes found to be elevated in the subject compared to a healthy control subject and / or increases the expression of one of more IRAK1 / 4-associated genes found to be decreased in the subject compared to a healthy control subject. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, decreases the expression of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 IRAK1 / 4-associated genes DB1 / 147901903.2 82 in the subject in need thereof. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, decreases the expression of one or more IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3 in the subject in need thereof. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, decreases the expression of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3 in the subject in need thereof. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, increases the expression of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 IRAK1 / 4-associated genes in the subject in need thereof. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, increases the expression of one or more IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, DB1 / 147901903.2 83 VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3 in the subject in need thereof. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, increases the expression of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3 in the subject in need thereof. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, decreases the secretion of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, or thirteen cytokines in the subject in need thereof. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, decreases the secretion of one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, or thirteen cytokines selected from: TNF-α, IL-1 β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, IL-23, GM-CSF, and IFN-γ. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, is administered to the subject in need thereof via parenteral administration, mucosal administration, intravenous administration, subcutaneous administration, topical administration, intradermal administration, oral administration, sublingual administration, intranasal administration, or intramuscular administration. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, is administered to the subject in need thereof in an amount of from about 0.005 mg / kg subject body weight to about 1,000 mg / kg subject body weight. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, is administered to the subject in a dosage of from about 1 µM to about 10,000 µM, about 1 µM to about 950 µM, about 1 µM to about 900 µM, about 1 µM to about 850 µM, about 1 µM to about 700 µM, about 1 µM to about 650 µM, about 1 µM to about 600 µM, about 1 µM to about 550 µM, DB1 / 147901903.2 84 about 1 µM to about 500 µM, about 1 µM to about 450 µM, about 1 µM to about 400 µM, about 1 µM to about 350 µM, about 1 µM to about 300 µM, about 1 µM to about 250 µM, about 1 µM to about 200 µM, about 1 µM to about 150 µM, about 1 µM to about 100 µM, or about 1 µM to about 50 µM. In one embodiment, a composition comprising Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, is administered to the subject in need thereof. In one embodiment, the composition comprising Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof further comprises one or more pharmaceutically acceptable carriers, excipients, or additives. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, is more effective at inhibiting cancer cell colony formation and / or cancer progenitor cell function when compared to a compound which inhibits IRAK1 without inhibiting IRAK4 or inhibits IRAK4 without inhibiting IRAK1. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, provides sustained treatment of the inflammatory disease / disorder, AML, or MDS in the subject. In one embodiment, the sustained treatment is greater than the treatment provided from a compound which inhibits IRAK1 without inhibiting IRAK4 or inhibits IRAK4 without inhibiting IRAK1. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, treats the inflammatory disease / disorder, AML, or MDS in the subject while the compound is administered to the subject. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, continues to treat the inflammatory disease / disorder, AML, or MDS in the subject after the administration is stopped. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, continues to treat the inflammatory disease / disorder, AML, or MDS in the subject for about 1 day, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, about one week, about two weeks, about three weeks, or about a month after the administration is stopped. In one embodiment, the method further comprises administering Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, in combination with one or more additional agents selected from: a chemotherapy agent, a BCL2 inhibitor, an immune modulator, a BTK inhibitor, a DNA methyltransferase inhibitor / hypomethylating agent, an anthracycline, a histone deacetylase (HDAC) inhibitor, a purine nucleoside analogue DB1 / 147901903.2 85 (antimetabolite), an isocitrate dehydrogenase 1 or 2 (IDH1 and / or IDH2) inhibitor, an antibody- drug conjugate, an mAbs / immunotherapy, a Plk inhibitor, a MEK inhibitor, a CDK inhibitor, a CDK9 inhibitor, a CDK8 inhibitor, a retinoic acid receptor agonist, a TP53 activator, a CELMoD, a smoothened receptor antagonist, an ERK inhibitor including an ERK2 / MAPK1 or ERK1 / MAPK3 inhibitor, a PI3K inhibitor, an mTOR inhibitor, a steroid or glucocorticoid, a steroid or glucocorticoid receptor modulator, an EZH2 inhibitor, a hedgehog (Hh) inhibitor, a Topoisomerase I inhibitor, a Topoisomerase II inhibitor, an aminopeptidase / Leukotriene A4 hydrolase inhibitor, a FLT3 / Axl / ALK inhibitor, a FLT3 / KIT / PDGFR, PKC, and / or KDR inhibitor, a Syk inhibitor, an E-selectin inhibitor, an NEDD8-activator, an MDM2 inhibitor, a PLK1 inhibitor, an Aura A inhibitor, an aurora kinase inhibitor, an EGFR inhibitor, an AuroraB / C / VEGFR1 / 2 / 3 / FLT3 / CSF-1R / Kit / PDGFRA / B inhibitor, an AKT 1, 2, and / or 3 inhibitor, a ABL1 / 2 / SRC / EPHA2 / LCK / YES1 / KIT / PDGFRB / FYN inhibitor, a farnesyltransferase inhibitor, a BRAF / MAP2K1 / MAP2K2 inhibitor, a Menin-KMT2A / MLL inhibitor, and a multikinase inhibitor. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, is administered to the subject in need thereof in combination with at least one of a BCL2 inhibitor, a BTK inhibitor, a gluococorticoid, a CDK inhibitor, and a DNA methyltransferase inhibitor. In one embodiment, the BCL2 inhibitor is venetoclax or a pharmaceutically acceptable salt thereof. In one embodiment, the BTK inhibitor is ibrutinib or a pharmaceutically acceptable salt thereof. In one embodiment, the glucocorticoid is selected from dexamethasone, methylprednisolone, prednisolone or a pharmaceutically acceptable salt of any one thereof. In one embodiment, the CDK inhibitor is a CDK4 inhibitor, a CDK6 inhibitor, a CDK7 inhibitor, and / or a CDK9 inhibitor. In one embodiment, the CDK inhibitor is selected from CDK4 / 6 inhibitor Palbociclib, CDK7 inhibitor THZ1, and / or CDK9 inhibitors BAY1251152 and Atuveciclib, or a pharmaceutically acceptable salt of any one thereof. In one embodiment, the DNA methyltransferase inhibitor is azacitidine or a pharmaceutically acceptable salt thereof. In one embodiment, one or more compositions comprising the one or more additional agents are administered to the subject in need thereof. In one embodiment, the one or more compositions comprising the one or more additional agents further comprise a pharmaceutically acceptable carrier, excipient, or additive. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, is administered DB1 / 147901903.2 86 sequentially with the one or more additional agents. In one embodiment, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, is administered concurrently with the one or more additional agents. In one embodiment, the composition comprising Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, is administered sequentially with the composition comprising the one or more additional agents. one embodiment, the composition comprising Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, is administered concurrently with the composition comprising the one or more additional agents. Clauses of the disclosure Clause 1. A method of treating an inflammatory disease or disorder or a cancer selected from acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in a subject in need thereof, the method comprising administering to the subject a compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof. Clause 1a. The method of clause 1, wherein the compound is Compound 8: or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof. Clause 2. The method of clause 1 or 1a, wherein the inflammatory disease or disorder is selected from chronic inflammation, sepsis, rheumatoid arthritis, hidradenitis suppurativa, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, psoriasis, Sjögren’s syndrome, Ankylosing spondylitis, systemic sclerosis, Type 1 diabetes mellitus, Crohn’s disease, and colitis. Clause 3. The method of clause 1 or 1a, wherein the acute myeloid leukemia (AML) is relapsed AML, refractory AML, relapsed / refractory AML, AML with resistance to hypomethylating DB1 / 147901903.2 87 agents, AML with resistance to venetoclax, AML with resistance to hypomethylating agents and venetoclax, monocytic AML, or monocytic-like AML. Clause 4. The method of any one of clauses 1, 1a, or 3, wherein the subject has acute myeloid leukemia (AML) and the subject has a gene mutation in one or more of FLT3, TET2, KIT, BCOR, BRAF, CDKN2A, UTX, ZRSR2, NPM1, PTEN, DNMT3A, EZH2, RUNX1, JAK2, ASXL1, ABL1, ATRX, BCORL1, KDM6A, PTPN11, TP53, CBL, CEBPA, FBXW7, HRAS, NRAS, IDH1, IDH2, NRAS, PDGFRA, SF3B1, ETV6, PHF6, GNAS, KRAS, NOTCH1, STAG2, SETBP1, GATA1, GATA2, WT1, SRSF2, GNAS, CEBPA, CALR, MPL, BCL11A, ATM, CTCF, U2AF1, TYK2, FBX, RUI, RAD21, or MLL3. Clause 5. The method of clause 1 or 1a, wherein the myelodysplastic syndrome (MDS) is MDS with a splicing factor mutation, MDS with a mutation in isocitrate dehydrogenase 1, or MDS with a mutation in isocitrate dehydrogenase 2. Clause 6. The method of any one of clauses 1, 1a, or 5, wherein the subject has myelodysplastic syndrome (MDS) and the subject has a gene mutation in one or more of U2AF1, FLT3, ASXL1, BCORL1, BRAF, CBL, CDKN2A, DNMT3A, FBXW7, GATA2, IDH2, KRAS, NOTCH1, NRAS, PDGFRA, PTEN, PTPN11, TET2, TP53, EZH2, HRAS, KIT, MPL, PHF6, RUNX1, WT1, ABL1, CEBPA, ETV6, IDH2, KDM6A, KIT, KRAS, PTEN, RUNX1, SF3B1, ZRSR2. Clause 7. The method of clause 5, wherein the MDS with a splicing factor mutation comprises MDS with a splicing factor mutation in U2AF1, SRSF2, SF3B1, or ZRSR2. Clause 8. The method of any one of clauses 1 to 7, wherein Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof has an IRAK1 IC50 of less than about 40 nM. Clause 8a. The method of any one of clauses 1 to 7, wherein Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof has an IRAK1 IC50of less than about 40 nM. Clause 9. The method of any one of clauses 1 to 8a, wherein Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, DB1 / 147901903.2 88 CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof has an IRAK4 IC50 of less than about 5 nM. Clause 9a. The method of any one of clauses 1 to 9, wherein Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof has an IRAK4 IC50 of less than about 5 nM. Clause 10. The method of any one of clauses 1 to 9a, wherein Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof has IRAK4:IRAK1 potency ratio of less than about 40. Clause 10a. The method of any one of clauses 1 to 10, wherein Compound 8, Compound 9, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof has IRAK4:IRAK1 potency ratio of less than about 40. Clause 11. The method of any one of clauses 1 to 10a, wherein Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof has an FLT3 IC50 of less than about 2.5 nM. Clause 11a. The method of any one of clauses 1 to 11, wherein Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof has an FLT3 IC50of less than about 2.5 nM. Clause 12. The method of any one of clauses 1 to 11, wherein the subject in need thereof has elevated expression of one or more IRAK1 / 4-associated genes and / or decreased expression of one or more IRAK1 / 4-associated genes. Clause 12a. The method of clause 12, wherein the subject in need thereof has elevated expression and / or decreased expression of one or more IRAK1 / 4-associated genes compared to a healthy control subject. Clause 13. The method of clause 12 or 12a, wherein the subject in need thereof has elevated expression of one or more IRAK1 / 4-associated genes selected from: PLS3, HSBP1L1, CDC42BPA, PPP2R3A, GNG12, PENK, STC2, DNAJC22, SH3D19, GABRD, RAVER2, ARHGEF26, APBB2, BAI2, DPEP1, LGI2, PIP5K1A, SOX18, BMP4, TMC4, KCNIP3, DB1 / 147901903.2 89 CCNO, ULK4P2, FAM57A, SCARA3, CERS1, BEND5, HAPLN3, DNMBP, KIAA1522, PIR, GTF3C5 ECHDC3, ICAM1, RAB3A, SDHA, C9orf116, MKI67, LMTK3, MCM10, ADM2, HSD17B14, LOC102724002, KCNH2, PRAME, KIAA1279, LOC101929974, ARHGAP21, SULT2B1, ADCY6, GBF1, TUBGCP2, CD19, SPIRE2, SH3PXD2B, AADAT, FOXC1, ZBED3, TSKU, NRARP, AMIGO2, PCBD1, TCAM1P, FAM57B, LOC101929021, PCK2, CCDC127, MGMT, C6orf147, TGFB1I1, DPP4, ALX4, TACC2, WLS, PACSIN3, NAPA-AS1, LINC00999, BAIAP3, ANKH, VDAC2, TAF3, ECHS1, EFNA3, CORO6, TCTN2, HPS1, DNAJB12, SPIB, SLC29A3, PHGDH, PTMS, TMEM91, SEC24C, HGD, MSS51, TEAD3, LARP4B, ZCCHC24, ARHGEF16, FOXO6, FBXO18, PPRC1, CCDC78, RHBDL1, SPINT1, STON2, NUDT8, NEBL, EPAS1, FAM178A, PI4K2A, SNED1, STAM, PLOD2, TM7SF2, FGD1, PCDHB6, CCNB3, MCMDC2, EDRF1, NRM, PPIF, ATF5, BRD9, B3GALT4, NET1, TMEM169, RPH3AL, DROSHA, RBMS2, POLR3A, TRIP13, LPHN1, ZMIZ1, RP11-344B5.2, HNRNPF, HSD17B7P2, SLIT1, LOC648987, ACTR1A, CCT5, S1PR5, WDFY4, GRK5, SREBF1, STXBP5L, VARS2, GAB2, ZFP36L1, CPNE7, HSPA2, NAT8L, DOK4, IGF1R, KHK, KIRREL2, COMTD1, ZNF488, CASC10, QRICH2, RBM17, LSS, PAX8, PKN3, HELLS, FN3K, CDC42EP1, NFIX, BMS1, STOX1, SEMA4B, SUPV3L1, FAM198A, RCOR2, PDCD4 PPAP2A, DDX12P, ACY3, TSPAN10, NUP155, RIBC2, PLCXD1, TP53INP2, GOLPH3, WDR70, BTRC, SVIL, DTX4, DUSP5, ECE1, MRPL43, SKP2, SNHG3, MYRF, ZFYVE27, H2AFY2, NOLC1, SLC25A28, WNK2, NDUFS6, SLC30A3, LOC642846, NEURL1B, ARMC4, SFXN3, VASH2, NOTUM, VCL, LOC100506901, CSTF2T, PRICKLE1, ZNF132, GPR153, ZMYND11, DGCR5, OXER1, VTI1A, PCDHGC3, MORC4, EIF3A, PDCD11, SLC38A1, MC1R, CBS, AC002454.1, PDCD6, B4GALNT1, RPP38, SUGT1P1, NEDD4L, PROCA1, SH3PXD2A, JAG2, FGFR3, TMEM191B, SEPHS1, LOC100505761, C21orf58, FADS1, TET1, GBGT1, KAT6B, KIFC2, TAF5, CASP7, PELI3, PP7080, ATN1, KIAA1598, FAM115A, NKX3-2, CHCHD10, GPSM1, LRP4, CDT1, EIF4EBP2, AASS, ABCC6P1, ABCD2, ADAMTS14, AGAP4, AGAP9, AIFM2, AKR1C1, AKR1E2, ANK3, ANKRD33B, ANO6, APBB1IP, ARHGAP19, ARNTL2, ARSG, ARTN, ASCC1, ASUN, BAG3, BEND4, BEX5, BLNK, BTAF1, C10orf10, C10orf12, C10orf76, C10orf91, C15orf38, C2CD4C, C2CD5, C3orf18, CALHM2, CAMK1D, CAPRIN2, CDH2, CDHR1, CEL, CEP72, CES3, CES4A, CHST3, CLIC5, CMAS, CNNM2, CNTN1, COL27A1, COL4A5, CPS1, CRABP1, CTBP2, DB1 / 147901903.2 90 CUEDC2, CXorf57, DAPK2, DDAH2, DDX11, DDX11-AS1, DENND5B, DHTKD1, DNM1L, DPCD, DPY19L2, DUSP5P1, EBF3, EFEMP2, EGFR, ELK1, EPHB4, FAM155B, FAM175B, FAM21C, FAM45A, FAM53B, FAM84B, FCER2, FGD4, FOXL2, FZD8, GAS1, GPC6, GRIA3, GUCY1B3, GYPE, HDHD3, HES4, HIF1AN, HMGCS1, HMX2, HMX3, HOXB13, HOXB6, HSD17B8, HSH2D, IDE, INPP5A, INPP5F, INPP5J, IPO8, IRAK4, ITPR2, ITPR3, JMJD1C, KAZALD1, KCNQ5, KCNS3, KIAA1324, KIF11, KLHL42, KLLN, KRAS, KREMEN2, LAT, LDB1, LGALS3BP, LINC00477, LIPE, LOC100288152, LOC100506688, LOC100506691, LOC100507487, LOC101927104, LOC101927799, LOC101928913, LOC102723337, LOC102724472, LPCAT1, LRMP, LRRC10B, LRRC20, LRRC27, LTK, LY6G5C, LZTS2, MAP2K6, MASTL, MCIDAS, MCMBP, MDGA2, METTL12, METTL20, MMS19, MPPED2, MRPS16, MRPS35, MSX1, MX1, NDUFB8, NEURL1, NEUROG3, NFKB2, NIM1K, NKD2, NLGN2, NNT, NNT-AS1, NT5DC2, NUDT13, OGDHL, OVOL2, OXCT1, P2RX7, P4HA1, PABPC1L, PANK1, PAOX, PAPD7, PAPSS2, PCDHB13, PCDHB14, PCED1B, PCED1B-AS1, PCSK5, PDLIM1, PEAR1, PFKP, PGAM1, PGAM4, PI15, PITX1, PLEKHA8P1, PLEKHO1, PPFIBP1, PPP2R2D, PPP3CB, PRTFDC1, PSTPIP2, PTENP1, PVRL3, PWWP2B, PXDC1, RNF208, ROBO1, RP11-184I16.4, RP11-53O19.1, RP11-96H19.1, RPAP3, RTN1, SAMD11, SAMD8, SCAF11, SCD5, SDHAP3, SEC14L2, SEC31B, SEC61A2, SECTM1, SFMBT2, SFXN2, SHANK3, SHISA3, SHISA7, SIDT1, SKIDA1, SLA2, SLC12A7, SLC16A6, SLC16A9, SLC4A11, SLITRK5, SMAD1, SNHG12, SNORA61, SNORD104, SOX1, SPEF2, SRRM3, SUFU, TARS, TCF7, TEX15, TGFBR3L, THBD, TIAL1, TLX3, TM7SF3, TMEM180, TMEM191C, TMEM255A, TMEM63C, TRIM72, TUBB3, TYSND1, UGT3A2, ULK2, UNC13D, USP54, VENTX, VIM, XPNPEP1, YARS2, YPEL3, ZDHHC16, ZDHHC6, ZNF43, ZNF438, ZNF503, ZNF503-AS2, ZNF511, ZNF574, ZNF622, ZNF726, ZNF99, ZWINT, ADM, ALDOC, BNIP3, CA3, CD209, CSMD3, DDIT4, FCGR2B, FCGR2C, FIGN, GLIS2, SHISA8, SOX5, TBC1D30, TLE6, TLX1, VAT1L, VEGFA, ANXA4, APLN, C1QL4, CCDC102A, CHDH, EGLN3, ENO2, FADS2, HK2, HSPA7 IL17RB, KLF2, LAMC, LINC00263, LOC101928092, LOC102724908, MIR210HG, NRTN, PFKFB4, SCD, SLC4A3, SLC6A8, ZNF215, and ZNF395. Clause 14. The method of any one of clauses 12, 12a, or 13, wherein the subject in need thereof has elevated expression of one or more IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, DB1 / 147901903.2 91 SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3. Clause 15. The method of clause 12 or 12a, wherein the subject in need thereof has decreased expression of one or more IRAK1 / 4-associated genes selected from: PLS3, HSBP1L1, CDC42BPA, PPP2R3A, GNG12, PENK, STC2, DNAJC22, SH3D19, GABRD, RAVER2, ARHGEF26, APBB2, BAI2, DPEP1, LGI2, PIP5K1A, SOX18, BMP4, TMC4, KCNIP3, CCNO, ULK4P2, FAM57A, SCARA3, CERS1, BEND5, HAPLN3, DNMBP, KIAA1522, PIR, GTF3C5 ECHDC3, ICAM1, RAB3A, SDHA, C9orf116, MKI67, LMTK3, MCM10, ADM2, HSD17B14, LOC102724002, KCNH2, PRAME, KIAA1279, LOC101929974, ARHGAP21, SULT2B1, ADCY6, GBF1, TUBGCP2, CD19, SPIRE2, SH3PXD2B, AADAT, FOXC1, ZBED3, TSKU, NRARP, AMIGO2, PCBD1, TCAM1P, FAM57B, LOC101929021, PCK2, CCDC127, MGMT, C6orf147, TGFB1I1, DPP4, ALX4, TACC2, WLS, PACSIN3, NAPA-AS1, LINC00999, BAIAP3, ANKH, VDAC2, TAF3, ECHS1, EFNA3, CORO6, TCTN2, HPS1, DNAJB12, SPIB, SLC29A3, PHGDH, PTMS, TMEM91, SEC24C, HGD, MSS51, TEAD3, LARP4B, ZCCHC24, ARHGEF16, FOXO6, FBXO18, PPRC1, CCDC78, RHBDL1, SPINT1, STON2, NUDT8, NEBL, EPAS1, FAM178A, PI4K2A, SNED1, STAM, PLOD2, TM7SF2, FGD1, PCDHB6, CCNB3, MCMDC2, EDRF1, NRM, PPIF, ATF5, BRD9, B3GALT4, NET1, TMEM169, RPH3AL, DROSHA, RBMS2, POLR3A, TRIP13, LPHN1, ZMIZ1, RP11-344B5.2, HNRNPF, HSD17B7P2, SLIT1, LOC648987, ACTR1A, CCT5, S1PR5, WDFY4, GRK5, SREBF1, STXBP5L, VARS2, GAB2, ZFP36L1, CPNE7, HSPA2, NAT8L, DOK4, IGF1R, KHK, KIRREL2, COMTD1, ZNF488, CASC10, QRICH2, RBM17, LSS, PAX8, PKN3, HELLS, FN3K, CDC42EP1, NFIX, BMS1, STOX1, SEMA4B, SUPV3L1, FAM198A, RCOR2, PDCD4, PPAP2A, DDX12P, ACY3, TSPAN10, NUP155, RIBC2, PLCXD1, TP53INP2, GOLPH3, WDR70, BTRC, SVIL, DTX4, DUSP5, ECE1, MRPL43, SKP2, SNHG3, MYRF, ZFYVE27, H2AFY2, NOLC1, SLC25A28, WNK2, NDUFS6, SLC30A3, LOC642846, NEURL1B, ARMC4, SFXN3, VASH2, NOTUM, VCL, LOC100506901, CSTF2T, PRICKLE1, ZNF132, GPR153, ZMYND11, DGCR5, OXER1, VTI1A, PCDHGC3, MORC4, EIF3A, PDCD11, SLC38A1, MC1R, CBS, AC002454.1, PDCD6, B4GALNT1, RPP38, SUGT1P1, DB1 / 147901903.2 92 NEDD4L, PROCA1, SH3PXD2A, JAG2, FGFR3, TMEM191B, SEPHS1, LOC100505761, C21orf58, FADS1, TET1, GBGT1, KAT6B, KIFC2, TAF5, CASP7, PELI3, PP7080, ATN1, KIAA1598, FAM115A, NKX3-2, CHCHD10, GPSM1, LRP4, CDT1, EIF4EBP2, AASS, ABCC6P1, ABCD2, ADAMTS14, AGAP4, AGAP9, AIFM2, AKR1C1, AKR1E2, ANK3, ANKRD33B, ANO6, APBB1IP, ARHGAP19, ARNTL2, ARSG, ARTN, ASCC1, ASUN, BAG3, BEND4, BEX5, BLNK, BTAF1, C10orf10, C10orf12, C10orf76, C10orf91, C15orf38, C2CD4C, C2CD5, C3orf18, CALHM2, CAMK1D, CAPRIN2, CDH2, CDHR1, CEL, CEP72, CES3, CES4A, CHST3, CLIC5, CMAS, CNNM2, CNTN1, COL27A1, COL4A5, CPS1, CRABP1, CTBP2, CUEDC2, CXorf57, DAPK2, DDAH2, DDX11, DDX11-AS1, DENND5B, DHTKD1, DNM1L, DPCD, DPY19L2, DUSP5P1, EBF3, EFEMP2, EGFR, ELK1, EPHB4, FAM155B, FAM175B, FAM21C, FAM45A, FAM53B, FAM84B, FCER2, FGD4, FOXL2, FZD8, GAS1, GPC6, GRIA3, GUCY1B3, GYPE, HDHD3, HES4, HIF1AN, HMGCS1, HMX2, HMX3, HOXB13, HOXB6, HSD17B8, HSH2D, IDE, INPP5A, INPP5F, INPP5J, IPO8, IRAK4, ITPR2, ITPR3, JMJD1C, KAZALD1, KCNQ5, KCNS3, KIAA1324, KIF11, KLHL42, KLLN, KRAS, KREMEN2, LAT, LDB1, LGALS3BP, LINC00477, LIPE, LOC100288152, LOC100506688, LOC100506691, LOC100507487, LOC101927104, LOC101927799, LOC101928913, LOC102723337, LOC102724472, LPCAT1, LRMP, LRRC10B, LRRC20, LRRC27, LTK, LY6G5C, LZTS2, MAP2K6, MASTL, MCIDAS, MCMBP, MDGA2, METTL12, METTL20, MMS19, MPPED2, MRPS16, MRPS35, MSX1, MX1, NDUFB8, NEURL1, NEUROG3, NFKB2, NIM1K, NKD2, NLGN2, NNT, NNT-AS1, NT5DC2, NUDT13, OGDHL, OVOL2, OXCT1, P2RX7, P4HA1, PABPC1L, PANK1, PAOX, PAPD7, PAPSS2, PCDHB13, PCDHB14, PCED1B, PCED1B-AS1, PCSK5, PDLIM1, PEAR1, PFKP, PGAM1, PGAM4, PI15, PITX1, PLEKHA8P1, PLEKHO1, PPFIBP1, PPP2R2D, PPP3CB, PRTFDC1, PSTPIP2, PTENP1, PVRL3, PWWP2B, PXDC1, RNF208, ROBO1, RP11- 184I16.4, RP11-53O19.1, RP11-96H19.1, RPAP3, RTN1, SAMD11, SAMD8, SCAF11, SCD5, SDHAP3, SEC14L2, SEC31B, SEC61A2, SECTM1, SFMBT2, SFXN2, SHANK3, SHISA3, SHISA7, SIDT1, SKIDA1, SLA2, SLC12A7, SLC16A6, SLC16A9, SLC4A11, SLITRK5, SMAD1, SNHG12, SNORA61, SNORD104, SOX1, SPEF2, SRRM3, SUFU, TARS, TCF7, TEX15, TGFBR3L, THBD, TIAL1, TLX3, TM7SF3, TMEM180, TMEM191C, TMEM255A, TMEM63C, TRIM72, TUBB3, TYSND1, UGT3A2, ULK2, UNC13D, USP54, VENTX, VIM, XPNPEP1, YARS2, YPEL3, ZDHHC16, ZDHHC6, ZNF43, ZNF438, ZNF503, ZNF503-AS2, DB1 / 147901903.2 93 ZNF511, ZNF574, ZNF622, ZNF726, ZNF99, ZWINT, ADM, ALDOC, BNIP3, CA3, CD209, CSMD3, DDIT4, FCGR2B, FCGR2C, FIGN, GLIS2, SHISA8, SOX5, TBC1D30, TLE6, TLX1, VAT1L, VEGFA, ANXA4, APLN, C1QL4, CCDC102A, CHDH, EGLN3, ENO2, FADS2, HK2, HSPA7, IL17RB, KLF2, LAMC, LINC00263, LOC101928092, LOC102724908, MIR210HG, NRTN, PFKFB4, SCD, SLC4A3, SLC6A8, ZNF215, and ZNF395. Clause 16. The method of any one of clauses 12, 12a, or 15, wherein the subject in need thereof has decreased expression of one or more IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3. Clause 17. The method of any one of clauses 1 to 16, wherein Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof decreases the expression of one of more IRAK1 / 4- associated genes in the subject and / or increases the expression of one of more IRAK1 / 4- associated genes in the subject. Clause 17a. The method of any one of clauses 1 to 16, wherein Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof decreases the expression of one of more IRAK1 / 4-associated genes found to be elevated in the subject and / or increases the expression of one of more IRAK1 / 4-associated genes found to be decreased in the subject. Clause 17b. The method of any one of clauses 1 to 17, wherein Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof decreases the expression of one of more IRAK1 / 4-associated genes found to be elevated in the subject and / or increases the expression of one of more IRAK1 / 4-associated genes found to be decreased in the subject. Clause 17c. The method of any one of clauses 17 to 17b, wherein the administration of DB1 / 147901903.2 94 Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof decreases the expression of the one or more IRAK1 / 4-associated genes found to be elevated in the subject before the administration of Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof, and / or increases the expression of the one or more IRAK1 / 4-associated genes found to be decreased in the subject before the administration of Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA- 4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof. Clause 17d. The method of any one of clauses 17, 17a, 17b, or 17c, wherein the administration of Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof decreases the expression of the one or more IRAK1 / 4-associated genes found to be elevated in the subject before the administration of Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, and / or increases the expression of the one or more IRAK1 / 4-associated genes found to be decreased in the subject before the administration of Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof. Clause 17e. The method of any one of clauses 17 to 17d, wherein the administration of Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA- 4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof decreases the expression of one or more IRAK1 / 4-associated genes found to be elevated in the subject compared to a healthy control subject, and / or increases the expression of one or more IRAK1 / 4-associated genes found to be decreased in the subject compared to a healthy control subject. Clause 17f. The method of any one of clauses 17 to 17e, wherein the administration of Compound 8, or a salt, ester, solvate, optical isomer, geometric DB1 / 147901903.2 95 isomer, or salt of an isomer thereof decreases the expression of one or more IRAK1 / 4-associated genes found to be elevated in the subject compared to a healthy control subject, and / or increases the expression of one or more IRAK1 / 4-associated genes found to be decreased in the subject compared to a healthy control subject. Clause 18. The method of any one of clauses 17 to 17f, wherein Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof decreases the expression of one or more IRAK1 / 4- associated genes selected from: PLS3, HSBP1L1, CDC42BPA, PPP2R3A, GNG12, PENK, STC2, DNAJC22, SH3D19, GABRD, RAVER2, ARHGEF26, APBB2, BAI2, DPEP1, LGI2, PIP5K1A, SOX18, BMP4, TMC4, KCNIP3, CCNO, ULK4P2, FAM57A, SCARA3, CERS1, BEND5, HAPLN3, DNMBP, KIAA1522, PIR, GTF3C5 ECHDC3, ICAM1, RAB3A, SDHA, C9orf116, MKI67, LMTK3, MCM10, ADM2, HSD17B14, LOC102724002, KCNH2, PRAME, KIAA1279, LOC101929974, ARHGAP21, SULT2B1, ADCY6, GBF1, TUBGCP2, CD19, SPIRE2, SH3PXD2B, AADAT, FOXC1, ZBED3, TSKU, NRARP, AMIGO2, PCBD1, TCAM1P, FAM57B, LOC101929021, PCK2, CCDC127, MGMT, C6orf147, TGFB1I1, DPP4, ALX4, TACC2, WLS, PACSIN3, NAPA-AS1, LINC00999, BAIAP3, ANKH, VDAC2, TAF3, ECHS1, EFNA3, CORO6, TCTN2, HPS1, DNAJB12, SPIB, SLC29A3, PHGDH, PTMS, TMEM91, SEC24C, HGD, MSS51, TEAD3, LARP4B, ZCCHC24, ARHGEF16, FOXO6, FBXO18, PPRC1, CCDC78, RHBDL1, SPINT1, STON2, NUDT8, NEBL, EPAS1, FAM178A, PI4K2A, SNED1, STAM, PLOD2, TM7SF2, FGD1, PCDHB6, CCNB3, MCMDC2, EDRF1, NRM, PPIF, ATF5, BRD9, B3GALT4, NET1, TMEM169, RPH3AL, DROSHA, RBMS2, POLR3A, TRIP13, LPHN1, ZMIZ1, RP11-344B5.2, HNRNPF, HSD17B7P2, SLIT1, LOC648987, ACTR1A, CCT5, S1PR5, WDFY4, GRK5, SREBF1, STXBP5L, VARS2, GAB2, ZFP36L1, CPNE7, HSPA2, NAT8L, DOK4, IGF1R, KHK, KIRREL2, COMTD1, ZNF488, CASC10, QRICH2, RBM17, LSS, PAX8, PKN3, HELLS, FN3K, CDC42EP1, NFIX, BMS1, STOX1, SEMA4B, SUPV3L1, FAM198A, RCOR2, PDCD4, PPAP2A, DDX12P, ACY3, TSPAN10, NUP155, RIBC2, PLCXD1, TP53INP2, GOLPH3, WDR70, BTRC, SVIL, DTX4, DUSP5, ECE1, MRPL43, SKP2, SNHG3, MYRF, ZFYVE27, H2AFY2, NOLC1, SLC25A28, WNK2, NDUFS6, SLC30A3, LOC642846, NEURL1B, ARMC4, SFXN3, VASH2, NOTUM, DB1 / 147901903.2 96 VCL, LOC100506901, CSTF2T, PRICKLE1, ZNF132, GPR153, ZMYND11, DGCR5, OXER1, VTI1A, PCDHGC3, MORC4, EIF3A, PDCD11, SLC38A1, MC1R, CBS, AC002454.1, PDCD6, B4GALNT1, RPP38, SUGT1P1, NEDD4L, PROCA1, SH3PXD2A, JAG2, FGFR3, TMEM191B, SEPHS1, LOC100505761, C21orf58, FADS1, TET1, GBGT1, KAT6B, KIFC2, TAF5, CASP7, PELI3, PP7080, ATN1, KIAA1598, FAM115A, NKX3-2, CHCHD10, GPSM1, LRP4, CDT1, EIF4EBP2, AASS, ABCC6P1, ABCD2, ADAMTS14, AGAP4, AGAP9, AIFM2, AKR1C1, AKR1E2, ANK3, ANKRD33B, ANO6, APBB1IP, ARHGAP19, ARNTL2, ARSG, ARTN, ASCC1, ASUN, BAG3, BEND4, BEX5, BLNK, BTAF1, C10orf10, C10orf12, C10orf76, C10orf91, C15orf38, C2CD4C, C2CD5, C3orf18, CALHM2, CAMK1D, CAPRIN2, CDH2, CDHR1, CEL, CEP72, CES3, CES4A, CHST3, CLIC5, CMAS, CNNM2, CNTN1, COL27A1, COL4A5, CPS1, CRABP1, CTBP2, CUEDC2, CXorf57, DAPK2, DDAH2, DDX11, DDX11-AS1, DENND5B, DHTKD1, DNM1L, DPCD, DPY19L2, DUSP5P1, EBF3, EFEMP2, EGFR, ELK1, EPHB4, FAM155B, FAM175B, FAM21C, FAM45A, FAM53B, FAM84B, FCER2, FGD4, FOXL2, FZD8, GAS1, GPC6, GRIA3, GUCY1B3, GYPE, HDHD3, HES4, HIF1AN, HMGCS1, HMX2, HMX3, HOXB13, HOXB6, HSD17B8, HSH2D, IDE, INPP5A, INPP5F, INPP5J, IPO8, IRAK4, ITPR2, ITPR3, JMJD1C, KAZALD1, KCNQ5, KCNS3, KIAA1324, KIF11, KLHL42, KLLN, KRAS, KREMEN2, LAT, LDB1, LGALS3BP, LINC00477, LIPE, LOC100288152, LOC100506688, LOC100506691, LOC100507487, LOC101927104, LOC101927799, LOC101928913, LOC102723337, LOC102724472, LPCAT1, LRMP, LRRC10B, LRRC20, LRRC27, LTK, LY6G5C, LZTS2, MAP2K6, MASTL, MCIDAS, MCMBP, MDGA2, METTL12, METTL20, MMS19, MPPED2, MRPS16, MRPS35, MSX1, MX1, NDUFB8, NEURL1, NEUROG3, NFKB2, NIM1K, NKD2, NLGN2, NNT, NNT-AS1, NT5DC2, NUDT13, OGDHL, OVOL2, OXCT1, P2RX7, P4HA1, PABPC1L, PANK1, PAOX, PAPD7, PAPSS2, PCDHB13, PCDHB14, PCED1B, PCED1B-AS1, PCSK5, PDLIM1, PEAR1, PFKP, PGAM1, PGAM4, PI15, PITX1, PLEKHA8P1, PLEKHO1, PPFIBP1, PPP2R2D, PPP3CB, PRTFDC1, PSTPIP2, PTENP1, PVRL3, PWWP2B, PXDC1, RNF208, ROBO1, RP11-184I16.4, RP11-53O19.1, RP11-96H19.1, RPAP3, RTN1, SAMD11, SAMD8, SCAF11, SCD5, SDHAP3, SEC14L2, SEC31B, SEC61A2, SECTM1, SFMBT2, SFXN2, SHANK3, SHISA3, SHISA7, SIDT1, SKIDA1, SLA2, SLC12A7, SLC16A6, SLC16A9, SLC4A11, SLITRK5, SMAD1, SNHG12, SNORA61, SNORD104, SOX1, SPEF2, SRRM3, SUFU, TARS, TCF7, TEX15, TGFBR3L, DB1 / 147901903.2 97 THBD, TIAL1, TLX3, TM7SF3, TMEM180, TMEM191C, TMEM255A, TMEM63C, TRIM72, TUBB3, TYSND1, UGT3A2, ULK2, UNC13D, USP54, VENTX, VIM, XPNPEP1, YARS2, YPEL3, ZDHHC16, ZDHHC6, ZNF43, ZNF438, ZNF503, ZNF503-AS2, ZNF511, ZNF574, ZNF622, ZNF726, ZNF99, ZWINT, ADM, ALDOC, BNIP3, CA3, CD209, CSMD3, DDIT4, FCGR2B, FCGR2C, FIGN, GLIS2, SHISA8, SOX5, TBC1D30, TLE6, TLX1, VAT1L, VEGFA, ANXA4, APLN, C1QL4, CCDC102A, CHDH, EGLN3, ENO2, FADS2, HK2, HSPA7 IL17RB, KLF2, LAMC, LINC00263, LOC101928092, LOC102724908, MIR210HG, NRTN, PFKFB4, SCD, SLC4A3, SLC6A8, ZNF215, and ZNF395. Clause 18a. The method of any one of clauses 17 to 18, wherein Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof decreases the expression of one or more IRAK1 / 4-associated genes selected from: PLS3, HSBP1L1, CDC42BPA, PPP2R3A, GNG12, PENK, STC2, DNAJC22, SH3D19, GABRD, RAVER2, ARHGEF26, APBB2, BAI2, DPEP1, LGI2, PIP5K1A, SOX18, BMP4, TMC4, KCNIP3, CCNO, ULK4P2, FAM57A, SCARA3, CERS1, BEND5, HAPLN3, DNMBP, KIAA1522, PIR, GTF3C5 ECHDC3, ICAM1, RAB3A, SDHA, C9orf116, MKI67, LMTK3, MCM10, ADM2, HSD17B14, LOC102724002, KCNH2, PRAME, KIAA1279, LOC101929974, ARHGAP21, SULT2B1, ADCY6, GBF1, TUBGCP2, CD19, SPIRE2, SH3PXD2B, AADAT, FOXC1, ZBED3, TSKU, NRARP, AMIGO2, PCBD1, TCAM1P, FAM57B, LOC101929021, PCK2, CCDC127, MGMT, C6orf147, TGFB1I1, DPP4, ALX4, TACC2, WLS, PACSIN3, NAPA-AS1, LINC00999, BAIAP3, ANKH, VDAC2, TAF3, ECHS1, EFNA3, CORO6, TCTN2, HPS1, DNAJB12, SPIB, SLC29A3, PHGDH, PTMS, TMEM91, SEC24C, HGD, MSS51, TEAD3, LARP4B, ZCCHC24, ARHGEF16, FOXO6, FBXO18, PPRC1, CCDC78, RHBDL1, SPINT1, STON2, NUDT8, NEBL, EPAS1, FAM178A, PI4K2A, SNED1, STAM, PLOD2, TM7SF2, FGD1, PCDHB6, CCNB3, MCMDC2, EDRF1, NRM, PPIF, ATF5, BRD9, B3GALT4, NET1, TMEM169, RPH3AL, DROSHA, RBMS2, POLR3A, TRIP13, LPHN1, ZMIZ1, RP11-344B5.2, HNRNPF, HSD17B7P2, SLIT1, LOC648987, ACTR1A, CCT5, S1PR5, WDFY4, GRK5, SREBF1, STXBP5L, VARS2, GAB2, ZFP36L1, CPNE7, HSPA2, NAT8L, DOK4, IGF1R, KHK, KIRREL2, COMTD1, ZNF488, CASC10, QRICH2, RBM17, LSS, PAX8, PKN3, HELLS, FN3K, CDC42EP1, NFIX, BMS1, STOX1, SEMA4B, SUPV3L1, FAM198A, RCOR2, PDCD4, PPAP2A, DDX12P, ACY3, TSPAN10, NUP155, RIBC2, PLCXD1, TP53INP2, GOLPH3, WDR70, BTRC, SVIL, DTX4, DUSP5, ECE1, MRPL43, SKP2, SNHG3, MYRF, ZFYVE27, DB1 / 147901903.2 98 H2AFY2, NOLC1, SLC25A28, WNK2, NDUFS6, SLC30A3, LOC642846, NEURL1B, ARMC4, SFXN3, VASH2, NOTUM, VCL, LOC100506901, CSTF2T, PRICKLE1, ZNF132, GPR153, ZMYND11, DGCR5, OXER1, VTI1A, PCDHGC3, MORC4, EIF3A, PDCD11, SLC38A1, MC1R, CBS, AC002454.1, PDCD6, B4GALNT1, RPP38, SUGT1P1, NEDD4L, PROCA1, SH3PXD2A, JAG2, FGFR3, TMEM191B, SEPHS1, LOC100505761, C21orf58, FADS1, TET1, GBGT1, KAT6B, KIFC2, TAF5, CASP7, PELI3, PP7080, ATN1, KIAA1598, FAM115A, NKX3-2, CHCHD10, GPSM1, LRP4, CDT1, EIF4EBP2, AASS, ABCC6P1, ABCD2, ADAMTS14, AGAP4, AGAP9, AIFM2, AKR1C1, AKR1E2, ANK3, ANKRD33B, ANO6, APBB1IP, ARHGAP19, ARNTL2, ARSG, ARTN, ASCC1, ASUN, BAG3, BEND4, BEX5, BLNK, BTAF1, C10orf10, C10orf12, C10orf76, C10orf91, C15orf38, C2CD4C, C2CD5, C3orf18, CALHM2, CAMK1D, CAPRIN2, CDH2, CDHR1, CEL, CEP72, CES3, CES4A, CHST3, CLIC5, CMAS, CNNM2, CNTN1, COL27A1, COL4A5, CPS1, CRABP1, CTBP2, CUEDC2, CXorf57, DAPK2, DDAH2, DDX11, DDX11-AS1, DENND5B, DHTKD1, DNM1L, DPCD, DPY19L2, DUSP5P1, EBF3, EFEMP2, EGFR, ELK1, EPHB4, FAM155B, FAM175B, FAM21C, FAM45A, FAM53B, FAM84B, FCER2, FGD4, FOXL2, FZD8, GAS1, GPC6, GRIA3, GUCY1B3, GYPE, HDHD3, HES4, HIF1AN, HMGCS1, HMX2, HMX3, HOXB13, HOXB6, HSD17B8, HSH2D, IDE, INPP5A, INPP5F, INPP5J, IPO8, IRAK4, ITPR2, ITPR3, JMJD1C, KAZALD1, KCNQ5, KCNS3, KIAA1324, KIF11, KLHL42, KLLN, KRAS, KREMEN2, LAT, LDB1, LGALS3BP, LINC00477, LIPE, LOC100288152, LOC100506688, LOC100506691, LOC100507487, LOC101927104, LOC101927799, LOC101928913, LOC102723337, LOC102724472, LPCAT1, LRMP, LRRC10B, LRRC20, LRRC27, LTK, LY6G5C, LZTS2, MAP2K6, MASTL, MCIDAS, MCMBP, MDGA2, METTL12, METTL20, MMS19, MPPED2, MRPS16, MRPS35, MSX1, MX1, NDUFB8, NEURL1, NEUROG3, NFKB2, NIM1K, NKD2, NLGN2, NNT, NNT-AS1, NT5DC2, NUDT13, OGDHL, OVOL2, OXCT1, P2RX7, P4HA1, PABPC1L, PANK1, PAOX, PAPD7, PAPSS2, PCDHB13, PCDHB14, PCED1B, PCED1B-AS1, PCSK5, PDLIM1, PEAR1, PFKP, PGAM1, PGAM4, PI15, PITX1, PLEKHA8P1, PLEKHO1, PPFIBP1, PPP2R2D, PPP3CB, PRTFDC1, PSTPIP2, PTENP1, PVRL3, PWWP2B, PXDC1, RNF208, ROBO1, RP11-184I16.4, RP11-53O19.1, RP11-96H19.1, RPAP3, RTN1, SAMD11, SAMD8, SCAF11, SCD5, SDHAP3, SEC14L2, SEC31B, SEC61A2, SECTM1, SFMBT2, SFXN2, SHANK3, SHISA3, SHISA7, SIDT1, SKIDA1, SLA2, SLC12A7, SLC16A6, SLC16A9, SLC4A11, SLITRK5, SMAD1, SNHG12, DB1 / 147901903.2 99 SNORA61, SNORD104, SOX1, SPEF2, SRRM3, SUFU, TARS, TCF7, TEX15, TGFBR3L, THBD, TIAL1, TLX3, TM7SF3, TMEM180, TMEM191C, TMEM255A, TMEM63C, TRIM72, TUBB3, TYSND1, UGT3A2, ULK2, UNC13D, USP54, VENTX, VIM, XPNPEP1, YARS2, YPEL3, ZDHHC16, ZDHHC6, ZNF43, ZNF438, ZNF503, ZNF503-AS2, ZNF511, ZNF574, ZNF622, ZNF726, ZNF99, ZWINT, ADM, ALDOC, BNIP3, CA3, CD209, CSMD3, DDIT4, FCGR2B, FCGR2C, FIGN, GLIS2, SHISA8, SOX5, TBC1D30, TLE6, TLX1, VAT1L, VEGFA, ANXA4, APLN, C1QL4, CCDC102A, CHDH, EGLN3, ENO2, FADS2, HK2, HSPA7 IL17RB, KLF2, LAMC, LINC00263, LOC101928092, LOC102724908, MIR210HG, NRTN, PFKFB4, SCD, SLC4A3, SLC6A8, ZNF215, and ZNF395. Clause 19. The method of any one of clauses 17 to 17f, 18, or 18a, wherein Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof decreases the expression of one or more IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3 in the subject. Clause 19a. The method of any one of clauses 17 to 17e, 18, 18a, or 19, wherein Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof decreases the expression of one or more IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3 in the subject. Clause 20. The method of any one of clauses 17 to 17f, wherein Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound DB1 / 147901903.2 100 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof increases the expression of one or more IRAK1 / 4- associated genes selected from: PLS3, HSBP1L1, CDC42BPA, PPP2R3A, GNG12, PENK, STC2, DNAJC22, SH3D19, GABRD, RAVER2, ARHGEF26, APBB2, BAI2, DPEP1, LGI2, PIP5K1A, SOX18, BMP4, TMC4, KCNIP3, CCNO, ULK4P2, FAM57A, SCARA3, CERS1, BEND5, HAPLN3, DNMBP, KIAA1522, PIR, GTF3C5 ECHDC3, ICAM1, RAB3A, SDHA, C9orf116, MKI67, LMTK3, MCM10, ADM2, HSD17B14, LOC102724002, KCNH2, PRAME, KIAA1279, LOC101929974, ARHGAP21, SULT2B1, ADCY6, GBF1, TUBGCP2, CD19, SPIRE2, SH3PXD2B, AADAT, FOXC1, ZBED3, TSKU, NRARP, AMIGO2, PCBD1, TCAM1P, FAM57B, LOC101929021, PCK2, CCDC127, MGMT, C6orf147, TGFB1I1, DPP4, ALX4, TACC2, WLS, PACSIN3, NAPA-AS1, LINC00999, BAIAP3, ANKH, VDAC2, TAF3, ECHS1, EFNA3, CORO6, TCTN2, HPS1, DNAJB12, SPIB, SLC29A3, PHGDH, PTMS, TMEM91, SEC24C, HGD, MSS51, TEAD3, LARP4B, ZCCHC24, ARHGEF16, FOXO6, FBXO18, PPRC1, CCDC78, RHBDL1, SPINT1, STON2, NUDT8, NEBL, EPAS1, FAM178A, PI4K2A, SNED1, STAM, PLOD2, TM7SF2, FGD1, PCDHB6, CCNB3, MCMDC2, EDRF1, NRM, PPIF, ATF5, BRD9, B3GALT4, NET1, TMEM169, RPH3AL, DROSHA, RBMS2, POLR3A, TRIP13, LPHN1, ZMIZ1, RP11-344B5.2, HNRNPF, HSD17B7P2, SLIT1, LOC648987, ACTR1A, CCT5, S1PR5, WDFY4, GRK5, SREBF1, STXBP5L, VARS2, GAB2, ZFP36L1, CPNE7, HSPA2, NAT8L, DOK4, IGF1R, KHK, KIRREL2, COMTD1, ZNF488, CASC10, QRICH2, RBM17, LSS, PAX8, PKN3, HELLS, FN3K, CDC42EP1, NFIX, BMS1, STOX1, SEMA4B, SUPV3L1, FAM198A, RCOR2, PDCD4, PPAP2A, DDX12P, ACY3, TSPAN10, NUP155, RIBC2, PLCXD1, TP53INP2, GOLPH3, WDR70, BTRC, SVIL, DTX4, DUSP5, ECE1, MRPL43, SKP2, SNHG3, MYRF, ZFYVE27, H2AFY2, NOLC1, SLC25A28, WNK2, NDUFS6, SLC30A3, LOC642846, NEURL1B, ARMC4, SFXN3, VASH2, NOTUM, VCL, LOC100506901, CSTF2T, PRICKLE1, ZNF132, GPR153, ZMYND11, DGCR5, OXER1, VTI1A, PCDHGC3, MORC4, EIF3A, PDCD11, SLC38A1, MC1R, CBS, AC002454.1, PDCD6, B4GALNT1, RPP38, SUGT1P1, NEDD4L, PROCA1, SH3PXD2A, JAG2, FGFR3, TMEM191B, SEPHS1, LOC100505761, C21orf58, FADS1, TET1, GBGT1, KAT6B, KIFC2, TAF5, CASP7, PELI3, PP7080, ATN1, KIAA1598, FAM115A, NKX3-2, CHCHD10, GPSM1, LRP4, CDT1, EIF4EBP2, AASS, ABCC6P1, ABCD2, ADAMTS14, AGAP4, AGAP9, AIFM2, DB1 / 147901903.2 101 AKR1C1, AKR1E2, ANK3, ANKRD33B, ANO6, APBB1IP, ARHGAP19, ARNTL2, ARSG, ARTN, ASCC1, ASUN, BAG3, BEND4, BEX5, BLNK, BTAF1, C10orf10, C10orf12, C10orf76, C10orf91, C15orf38, C2CD4C, C2CD5, C3orf18, CALHM2, CAMK1D, CAPRIN2, CDH2, CDHR1, CEL, CEP72, CES3, CES4A, CHST3, CLIC5, CMAS, CNNM2, CNTN1, COL27A1, COL4A5, CPS1, CRABP1, CTBP2, CUEDC2, CXorf57, DAPK2, DDAH2, DDX11, DDX11-AS1, DENND5B, DHTKD1, DNM1L, DPCD, DPY19L2, DUSP5P1, EBF3, EFEMP2, EGFR, ELK1, EPHB4, FAM155B, FAM175B, FAM21C, FAM45A, FAM53B, FAM84B, FCER2, FGD4, FOXL2, FZD8, GAS1, GPC6, GRIA3, GUCY1B3, GYPE, HDHD3, HES4, HIF1AN, HMGCS1, HMX2, HMX3, HOXB13, HOXB6, HSD17B8, HSH2D, IDE, INPP5A, INPP5F, INPP5J, IPO8, IRAK4, ITPR2, ITPR3, JMJD1C, KAZALD1, KCNQ5, KCNS3, KIAA1324, KIF11, KLHL42, KLLN, KRAS, KREMEN2, LAT, LDB1, LGALS3BP, LINC00477, LIPE, LOC100288152, LOC100506688, LOC100506691, LOC100507487, LOC101927104, LOC101927799, LOC101928913, LOC102723337, LOC102724472, LPCAT1, LRMP, LRRC10B, LRRC20, LRRC27, LTK, LY6G5C, LZTS2, MAP2K6, MASTL, MCIDAS, MCMBP, MDGA2, METTL12, METTL20, MMS19, MPPED2, MRPS16, MRPS35, MSX1, MX1, NDUFB8, NEURL1, NEUROG3, NFKB2, NIM1K, NKD2, NLGN2, NNT, NNT-AS1, NT5DC2, NUDT13, OGDHL, OVOL2, OXCT1, P2RX7, P4HA1, PABPC1L, PANK1, PAOX, PAPD7, PAPSS2, PCDHB13, PCDHB14, PCED1B, PCED1B-AS1, PCSK5, PDLIM1, PEAR1, PFKP, PGAM1, PGAM4, PI15, PITX1, PLEKHA8P1, PLEKHO1, PPFIBP1, PPP2R2D, PPP3CB, PRTFDC1, PSTPIP2, PTENP1, PVRL3, PWWP2B, PXDC1, RNF208, ROBO1, RP11-184I16.4, RP11-53O19.1, RP11-96H19.1, RPAP3, RTN1, SAMD11, SAMD8, SCAF11, SCD5, SDHAP3, SEC14L2, SEC31B, SEC61A2, SECTM1, SFMBT2, SFXN2, SHANK3, SHISA3, SHISA7, SIDT1, SKIDA1, SLA2, SLC12A7, SLC16A6, SLC16A9, SLC4A11, SLITRK5, SMAD1, SNHG12, SNORA61, SNORD104, SOX1, SPEF2, SRRM3, SUFU, TARS, TCF7, TEX15, TGFBR3L, THBD, TIAL1, TLX3, TM7SF3, TMEM180, TMEM191C, TMEM255A, TMEM63C, TRIM72, TUBB3, TYSND1, UGT3A2, ULK2, UNC13D, USP54, VENTX, VIM, XPNPEP1, YARS2, YPEL3, ZDHHC16, ZDHHC6, ZNF43, ZNF438, ZNF503, ZNF503-AS2, ZNF511, ZNF574, ZNF622, ZNF726, ZNF99, ZWINT, ADM, ALDOC, BNIP3, CA3, CD209, CSMD3, DDIT4, FCGR2B, FCGR2C, FIGN, GLIS2, SHISA8, SOX5, TBC1D30, TLE6, TLX1, VAT1L, VEGFA, ANXA4, APLN, C1QL4, CCDC102A, CHDH, EGLN3, ENO2, FADS2, HK2, HSPA7 DB1 / 147901903.2 102 IL17RB, KLF2, LAMC, LINC00263, LOC101928092, LOC102724908, MIR210HG, NRTN, PFKFB4, SCD, SLC4A3, SLC6A8, ZNF215, and ZNF395. Clause 20a. The method of any one of clauses 17 to 17f or 20, wherein Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof increases the expression of one or more IRAK1 / 4-associated genes selected from: PLS3, HSBP1L1, CDC42BPA, PPP2R3A, GNG12, PENK, STC2, DNAJC22, SH3D19, GABRD, RAVER2, ARHGEF26, APBB2, BAI2, DPEP1, LGI2, PIP5K1A, SOX18, BMP4, TMC4, KCNIP3, CCNO, ULK4P2, FAM57A, SCARA3, CERS1, BEND5, HAPLN3, DNMBP, KIAA1522, PIR, GTF3C5 ECHDC3, ICAM1, RAB3A, SDHA, C9orf116, MKI67, LMTK3, MCM10, ADM2, HSD17B14, LOC102724002, KCNH2, PRAME, KIAA1279, LOC101929974, ARHGAP21, SULT2B1, ADCY6, GBF1, TUBGCP2, CD19, SPIRE2, SH3PXD2B, AADAT, FOXC1, ZBED3, TSKU, NRARP, AMIGO2, PCBD1, TCAM1P, FAM57B, LOC101929021, PCK2, CCDC127, MGMT, C6orf147, TGFB1I1, DPP4, ALX4, TACC2, WLS, PACSIN3, NAPA-AS1, LINC00999, BAIAP3, ANKH, VDAC2, TAF3, ECHS1, EFNA3, CORO6, TCTN2, HPS1, DNAJB12, SPIB, SLC29A3, PHGDH, PTMS, TMEM91, SEC24C, HGD, MSS51, TEAD3, LARP4B, ZCCHC24, ARHGEF16, FOXO6, FBXO18, PPRC1, CCDC78, RHBDL1, SPINT1, STON2, NUDT8, NEBL, EPAS1, FAM178A, PI4K2A, SNED1, STAM, PLOD2, TM7SF2, FGD1, PCDHB6, CCNB3, MCMDC2, EDRF1, NRM, PPIF, ATF5, BRD9, B3GALT4, NET1, TMEM169, RPH3AL, DROSHA, RBMS2, POLR3A, TRIP13, LPHN1, ZMIZ1, RP11-344B5.2, HNRNPF, HSD17B7P2, SLIT1, LOC648987, ACTR1A, CCT5, S1PR5, WDFY4, GRK5, SREBF1, STXBP5L, VARS2, GAB2, ZFP36L1, CPNE7, HSPA2, NAT8L, DOK4, IGF1R, KHK, KIRREL2, COMTD1, ZNF488, CASC10, QRICH2, RBM17, LSS, PAX8, PKN3, HELLS, FN3K, CDC42EP1, NFIX, BMS1, STOX1, SEMA4B, SUPV3L1, FAM198A, RCOR2, PDCD4, PPAP2A, DDX12P, ACY3, TSPAN10, NUP155, RIBC2, PLCXD1, TP53INP2, GOLPH3, WDR70, BTRC, SVIL, DTX4, DUSP5, ECE1, MRPL43, SKP2, SNHG3, MYRF, ZFYVE27, H2AFY2, NOLC1, SLC25A28, WNK2, NDUFS6, SLC30A3, LOC642846, NEURL1B, ARMC4, SFXN3, VASH2, NOTUM, VCL, LOC100506901, CSTF2T, PRICKLE1, ZNF132, GPR153, ZMYND11, DGCR5, OXER1, VTI1A, PCDHGC3, MORC4, EIF3A, PDCD11, SLC38A1, MC1R, CBS, AC002454.1, PDCD6, B4GALNT1, RPP38, SUGT1P1, NEDD4L, PROCA1, SH3PXD2A, JAG2, FGFR3, TMEM191B, SEPHS1, LOC100505761, C21orf58, FADS1, TET1, GBGT1, KAT6B, KIFC2, TAF5, CASP7, PELI3, PP7080, ATN1, DB1 / 147901903.2 103 KIAA1598, FAM115A, NKX3-2, CHCHD10, GPSM1, LRP4, CDT1, EIF4EBP2, AASS, ABCC6P1, ABCD2, ADAMTS14, AGAP4, AGAP9, AIFM2, AKR1C1, AKR1E2, ANK3, ANKRD33B, ANO6, APBB1IP, ARHGAP19, ARNTL2, ARSG, ARTN, ASCC1, ASUN, BAG3, BEND4, BEX5, BLNK, BTAF1, C10orf10, C10orf12, C10orf76, C10orf91, C15orf38, C2CD4C, C2CD5, C3orf18, CALHM2, CAMK1D, CAPRIN2, CDH2, CDHR1, CEL, CEP72, CES3, CES4A, CHST3, CLIC5, CMAS, CNNM2, CNTN1, COL27A1, COL4A5, CPS1, CRABP1, CTBP2, CUEDC2, CXorf57, DAPK2, DDAH2, DDX11, DDX11-AS1, DENND5B, DHTKD1, DNM1L, DPCD, DPY19L2, DUSP5P1, EBF3, EFEMP2, EGFR, ELK1, EPHB4, FAM155B, FAM175B, FAM21C, FAM45A, FAM53B, FAM84B, FCER2, FGD4, FOXL2, FZD8, GAS1, GPC6, GRIA3, GUCY1B3, GYPE, HDHD3, HES4, HIF1AN, HMGCS1, HMX2, HMX3, HOXB13, HOXB6, HSD17B8, HSH2D, IDE, INPP5A, INPP5F, INPP5J, IPO8, IRAK4, ITPR2, ITPR3, JMJD1C, KAZALD1, KCNQ5, KCNS3, KIAA1324, KIF11, KLHL42, KLLN, KRAS, KREMEN2, LAT, LDB1, LGALS3BP, LINC00477, LIPE, LOC100288152, LOC100506688, LOC100506691, LOC100507487, LOC101927104, LOC101927799, LOC101928913, LOC102723337, LOC102724472, LPCAT1, LRMP, LRRC10B, LRRC20, LRRC27, LTK, LY6G5C, LZTS2, MAP2K6, MASTL, MCIDAS, MCMBP, MDGA2, METTL12, METTL20, MMS19, MPPED2, MRPS16, MRPS35, MSX1, MX1, NDUFB8, NEURL1, NEUROG3, NFKB2, NIM1K, NKD2, NLGN2, NNT, NNT-AS1, NT5DC2, NUDT13, OGDHL, OVOL2, OXCT1, P2RX7, P4HA1, PABPC1L, PANK1, PAOX, PAPD7, PAPSS2, PCDHB13, PCDHB14, PCED1B, PCED1B-AS1, PCSK5, PDLIM1, PEAR1, PFKP, PGAM1, PGAM4, PI15, PITX1, PLEKHA8P1, PLEKHO1, PPFIBP1, PPP2R2D, PPP3CB, PRTFDC1, PSTPIP2, PTENP1, PVRL3, PWWP2B, PXDC1, RNF208, ROBO1, RP11-184I16.4, RP11-53O19.1, RP11-96H19.1, RPAP3, RTN1, SAMD11, SAMD8, SCAF11, SCD5, SDHAP3, SEC14L2, SEC31B, SEC61A2, SECTM1, SFMBT2, SFXN2, SHANK3, SHISA3, SHISA7, SIDT1, SKIDA1, SLA2, SLC12A7, SLC16A6, SLC16A9, SLC4A11, SLITRK5, SMAD1, SNHG12, SNORA61, SNORD104, SOX1, SPEF2, SRRM3, SUFU, TARS, TCF7, TEX15, TGFBR3L, THBD, TIAL1, TLX3, TM7SF3, TMEM180, TMEM191C, TMEM255A, TMEM63C, TRIM72, TUBB3, TYSND1, UGT3A2, ULK2, UNC13D, USP54, VENTX, VIM, XPNPEP1, YARS2, YPEL3, ZDHHC16, ZDHHC6, ZNF43, ZNF438, ZNF503, ZNF503-AS2, ZNF511, ZNF574, ZNF622, ZNF726, ZNF99, ZWINT, ADM, ALDOC, BNIP3, CA3, CD209, CSMD3, DDIT4, DB1 / 147901903.2 104 FCGR2B, FCGR2C, FIGN, GLIS2, SHISA8, SOX5, TBC1D30, TLE6, TLX1, VAT1L, VEGFA, ANXA4, APLN, C1QL4, CCDC102A, CHDH, EGLN3, ENO2, FADS2, HK2, HSPA7 IL17RB, KLF2, LAMC, LINC00263, LOC101928092, LOC102724908, MIR210HG, NRTN, PFKFB4, SCD, SLC4A3, SLC6A8, ZNF215, and ZNF395. Clause 21. The method of any one of clauses 17 to 17f, 20, or 20a, wherein Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof increases the expression of one or more IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3 in the subject. Clause 21a. The method of any one of clauses 17 to 17f, 20, 20a, or 21 wherein Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof increases the expression of one or more IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3 in the subject. Clause 22. The method of any one of clauses 1 to 21a, wherein the subject in need thereof has elevated expression of one or more NFκB-associated genes and / or decreased expression of one or more NFκB-associated genes. Clause 22a. The method of clause 22, wherein the subject in need thereof has elevated expression of one or more NFκB-associated genes compared to a healthy control subject, and / or decreased expression of one or more NFκB-associated genes compared to a healthy control subject. DB1 / 147901903.2 105 Clause 23. The method of clause 22 or 22a, wherein the subject in need thereof has elevated expression of one or more NFκB-associated genes selected from: A4, ABCA1, ABCB1, ABCB4, ABCB9, ABCC6, ABCG5, ABCG8, ADAM19, ADH1A, ADORA1, ADORA2A, ADRA2B. AFP, AGER, AGT, AHCTF1, AICDA, AKR1C1, ALOX12, ALOX5, AMACR, AMH, ANGPT1, APOBEC2, APOC3, APOD, APOE, AQP4, AR, ARFRP1, ART1, ASPH, ASS1, ATP1A2, B2M, BACE1, BAX, BCL2, BCL2A1, BCL2L1, BCL2L11, BCL3, BDKRB1, BDKRB1, BDNF, BGN, BLIMP1 / PRDM1, BLNK, BLR1, BMI1, BMP2, BMP4, BNIP3, BRCA2, BTK, C3, C4A, C4BPA, C69, CALCB, CASP4, CAV1, CCL1, CCL15, CCL17, CCL19, CCL2, CCL20, CCL22, CCL23, CCL28, CCL3, CCL4, CCL5, CCND1, CCND2, CCND3, CCR5, CCR7, CD209, CD274, CD38, CD3G, CD40, CD40LG, CD44, CD48, CD54, CD80, CD83, CD86, CDK6, CDKN1A, CDX1, CEBPD, CFB, CFLAR, CGM3, CHI3L1, CIDEA, CLDN2, COL1A2, CR2, CREB3, CRP, CSF1, CSF2, CSF3, CTSB, CTSL1, CXCL1, CXCL10, CXCL11, CXCL3, CXCL5, CXCL6, CXCL9, CYP19A1, CYP27B1, CYP2C11, CYP2E1, CYP7B1, DCTN4, DEFB2, DIO2, DMP1, DNASE1L2, DPYD, DUSP1, E2F3, EBI3, EDN1, EGFR, EGR1, ELF3, ENG, ENO2, EPHA1, EPO, ERBB2, ERVWE1, F11R, F3, F8, FABP6, FAM148A, FAS, FASLG, FCER2. FCER2 / CD23, FCGRT, FGF8, FN1, FOS, FSTL3, FTH1, G6PC, G6PD, GAD1, GADD45B, GATA3, GBP1, GCLC, GCLM, GCNT1, GJB1, GNAI2, GNB2L1, GNRH2, GRIN1, GRIN2A, GRM2, GRO-beta, GRO-gamma, GSTP1, GUCY1A2, GZMB, HAMP, HAS1, HBE1, HBZ, HGF, HIF1A, HLA-B, HLA-G, HMGN1, HMOX1, HOXA9, HPSE, HSD11B2, HSD17B8, HSP90AA1, ICOS, IDO1, IER2, IER3, IFI44L, IFNB, IFNG, IGFBP1, IGFBP2, IGHE, IGHG1, IGHG2, IGHG4, IGKC, Iigp1, IL10, IL11, IL12A, IL12B, IL13, IL15, IL17, IL1A, IL1B, IL1RN, IL2, IL23A, IL27, IL2RA, IL6, IL8, IL8RA, IL8RB, IL9, INHBA, IRF1, IRF2, IRF4, IRF7, JMJD3, JUNB, KC, KCNK5, KCNN2, KISS1, KITLG, KLF10, KLK3, KLRA1, KRT15, KRT3, KRT5, KRT6B, LAMB2, LBP, LCN2, LEF1, LGALS3, LIPG, LTA, LTB, LTF, LYZ, MADCAM1, MAP4K1, MBP, MDK, MMP1, MMP3, MMP9, MT3, MTHFR, MUC2, MX1, MYB, MYC, MYLK, MYOZ1, NCAM, NFKB1, NFKB2, NFKBIA, NFKBIE, NFKBIZ, NGFB, NK4, NLRP2, NOD2, NOS1, NOS2A, NOX1, NPY1R, NQO1, NR3C1, NR4A2, NRG1, NUAK2, OLR1, OPN1SW, OPRD1, OPRM1, ORM1, Osterix, OXTR, PAFAH2, PAX8, PDE7A, PDGFB, PDYN, PENK, PGK1, PGLYRP1, PGR, PI3KAP1, PIGF, pIgR, PIK3CA, PIM1, PLA2, PLAU, PLCD1, PLK3, POMC, DB1 / 147901903.2 106 PPARGC1B, PPP5C, PRF1, PRKACA, PRKCD, PRL, PSMB9, PSME1, PSME2, PTAFR,, PTEN, PTGDS, PTGES, PTGIS, PTGS2, PTHLH, PTPN1, PTPN13, PTS, PTX3, PYCARD, RAG1, RAG2, RBBP4, Rdh1, Rdh7, REL, RELB, REV3L, RIPK2, S100A10, S100A4, S100A6, SAA1, SAA2, SAA, SAT1, SCNN1A, SDC4, SELE, SELP, SELS, SENP2, SERPINA1, SERPINA2, SERPINA3, SERPINB1, SERPINE1, PAI-1, SERPINE2, SH3BGRL, SKALP, PI3, SKP2, SLC11A2, SLC16A1, SLC3A2, SLC6A6, Slfn2, SNAI1, SOD1, SOD2, SOX9, SPATA19, SPI1, SPP1, ST6GAL1, ST8SIA1, STAT5A, SUPV3L1, TACR1, TAP1, TAPBP, TCRB, TERT, TF, TFEC, TFF3, TFPI2, TGM1, TGM2, THBS1, THBS2, TICAM1, TIFA, TLR2, TLR9, TNC, TN, TNFAIP2, TNFAIP3, TNFRSF1B, TNFRSF4, TNFRSF9, TNFSF10, TNFSF13B, TNFSF13B, TNFSF15, TNIP1, TNIP3, TP53, TRAF1, TRAF2, TREM1, TRPC1, TWIST1, UBE2M, UCP2, UGCGL1, UPK1B, UPP1, VCAM1, VEGFC, VIM, VPS53, WNT10B, WT1, XDH, XIAP, YY1, and ZNF366. Clause 24. The method of clause 22 or 22a, wherein the subject in need thereof has decreased expression of one or more NFκB-associated genes selected from: A4, ABCA1, ABCB1, ABCB4, ABCB9, ABCC6, ABCG5, ABCG8, ADAM19, ADH1A, ADORA1, ADORA2A, ADRA2B. AFP, AGER, AGT, AHCTF1, AICDA, AKR1C1, ALOX12, ALOX5, AMACR, AMH, ANGPT1, APOBEC2, APOC3, APOD, APOE, AQP4, AR, ARFRP1, ART1, ASPH, ASS1, ATP1A2, B2M, BACE1, BAX, BCL2, BCL2A1, BCL2L1, BCL2L11, BCL3, BDKRB1, BDKRB1, BDNF, BGN, BLIMP1 / PRDM1, BLNK, BLR1, BMI1, BMP2, BMP4, BNIP3, BRCA2, BTK, C3, C4A, C4BPA, C69, CALCB, CASP4, CAV1, CCL1, CCL15, CCL17, CCL19, CCL2, CCL20, CCL22, CCL23, CCL28, CCL3, CCL4, CCL5, CCND1, CCND2, CCND3, CCR5, CCR7, CD209, CD274, CD38, CD3G, CD40, CD40LG, CD44, CD48, CD54, CD80, CD83, CD86, CDK6, CDKN1A, CDX1, CEBPD, CFB, CFLAR, CGM3, CHI3L1, CIDEA, CLDN2, COL1A2, CR2, CREB3, CRP, CSF1, CSF2, CSF3, CTSB, CTSL1, CXCL1, CXCL10, CXCL11, CXCL3, CXCL5, CXCL6, CXCL9, CYP19A1, CYP27B1, CYP2C11, CYP2E1, CYP7B1, DCTN4, DEFB2, DIO2, DMP1, DNASE1L2, DPYD, DUSP1, E2F3, EBI3, EDN1, EGFR, EGR1, ELF3, ENG, ENO2, EPHA1, EPO, ERBB2, ERVWE1, F11R, F3, F8, FABP6, FAM148A, FAS, FASLG, FCER2. FCER2 / CD23, FCGRT, FGF8, FN1, FOS, FSTL3, FTH1, G6PC, G6PD, GAD1, GADD45B, GATA3, GBP1, GCLC, GCLM, GCNT1, GJB1, GNAI2, GNB2L1, GNRH2, GRIN1, GRIN2A, GRM2, GRO-beta, GRO-gamma, GSTP1, GUCY1A2, GZMB, HAMP, HAS1, HBE1, HBZ, HGF, HIF1A, HLA-B, HLA-G, HMGN1, DB1 / 147901903.2 107 HMOX1, HOXA9, HPSE, HSD11B2, HSD17B8, HSP90AA1, ICOS, IDO1, IER2, IER3, IFI44L, IFNB, IFNG, IGFBP1, IGFBP2, IGHE, IGHG1, IGHG2, IGHG4, IGKC, Iigp1, IL10, IL11, IL12A, IL12B, IL13, IL15, IL17, IL1A, IL1B, IL1RN, IL2, IL23A, IL27, IL2RA, IL6, IL8, IL8RA, IL8RB, IL9, INHBA, IRF1, IRF2, IRF4, IRF7, JMJD3, JUNB, KC, KCNK5, KCNN2, KISS1, KITLG, KLF10, KLK3, KLRA1, KRT15, KRT3, KRT5, KRT6B, LAMB2, LBP, LCN2, LEF1, LGALS3, LIPG, LTA, LTB, LTF, LYZ, MADCAM1, MAP4K1, MBP, MDK, MMP1, MMP3, MMP9, MT3, MTHFR, MUC2, MX1, MYB, MYC, MYLK, MYOZ1, NCAM, NFKB1, NFKB2, NFKBIA, NFKBIE, NFKBIZ, NGFB, NK4, NLRP2, NOD2, NOS1, NOS2A, NOX1, NPY1R, NQO1, NR3C1, NR4A2, NRG1, NUAK2, OLR1, OPN1SW, OPRD1, OPRM1, ORM1, Osterix, OXTR, PAFAH2, PAX8, PDE7A, PDGFB, PDYN, PENK, PGK1, PGLYRP1, PGR, PI3KAP1, PIGF, pIgR, PIK3CA, PIM1, PLA2, PLAU, PLCD1, PLK3, POMC, PPARGC1B, PPP5C, PRF1, PRKACA, PRKCD, PRL, PSMB9, PSME1, PSME2, PTAFR,, PTEN, PTGDS, PTGES, PTGIS, PTGS2, PTHLH, PTPN1, PTPN13, PTS, PTX3, PYCARD, RAG1, RAG2, RBBP4, Rdh1, Rdh7, REL, RELB, REV3L, RIPK2, S100A10, S100A4, S100A6, SAA1, SAA2, SAA, SAT1, SCNN1A, SDC4, SELE, SELP, SELS, SENP2, SERPINA1, SERPINA2, SERPINA3, SERPINB1, SERPINE1, PAI-1, SERPINE2, SH3BGRL, SKALP, PI3, SKP2, SLC11A2, SLC16A1, SLC3A2, SLC6A6, Slfn2, SNAI1, SOD1, SOD2, SOX9, SPATA19, SPI1, SPP1, ST6GAL1, ST8SIA1, STAT5A, SUPV3L1, TACR1, TAP1, TAPBP, TCRB, TERT, TF, TFEC, TFF3, TFPI2, TGM1, TGM2, THBS1, THBS2, TICAM1, TIFA, TLR2, TLR9, TNC, TN, TNFAIP2, TNFAIP3, TNFRSF1B, TNFRSF4, TNFRSF9, TNFSF10, TNFSF13B, TNFSF13B, TNFSF15, TNIP1, TNIP3, TP53, TRAF1, TRAF2, TREM1, TRPC1, TWIST1, UBE2M, UCP2, UGCGL1, UPK1B, UPP1, VCAM1, VEGFC, VIM, VPS53, WNT10B, WT1, XDH, XIAP, YY1, and ZNF366. Clause 25. The method of any one of clauses 1 to 24, wherein the administration of Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof decreases the expression of one of more NFκB-associated genes found to be elevated in the subject and / or increases the expression of one of more NFκB-associated genes found to be decreased in the subject. Clause 25a. The method of any one of clauses 1 to 25, wherein the administration of DB1 / 147901903.2 108 Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, decreases the expression of one of more NFκB-associated genes found to be elevated in the subject and / or increases the expression of one of more NFκB-associated genes found to be decreased in the subject. Clause 25b. The method of clause 25 or 25a, wherein the administration of Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof, decreases the expression of the one or more NFκB-associated genes found to be elevated in the subject before the administration of Compound 8, and / or increases the expression of the one or more NFκB-associated genes found to be decreased in the subject before the administration of Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof. Clause 25c. The method of any one of clauses 25, 25a, or 25b, wherein the administration of Compound 8 decreases the expression of the one or more NFκB-associated genes found to be elevated in the subject before the administration of Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, and / or increases the expression of the one or more NFκB-associated genes found to be decreased in the subject before the administration of Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof. Clause 25d. The method of any one of clauses 25 to 25c, wherein upon administration to the subject, Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof, decreases the expression of one or more NFκB-associated genes found to be elevated in the subject compared to a healthy control subject, and / or increases the expression of one or more NFκB-associated genes found to be decreased in the subject compared to a healthy control subject. Clause 25e. The method of any one of clauses 25 to 25d, wherein upon administration to the subject, Compound 8, or a salt, ester, solvate, optical isomer, DB1 / 147901903.2 109 geometric isomer, or salt of an isomer thereof, decreases the expression of one or more NFκB- associated genes found to be elevated in the subject compared to a healthy control subject, and / or increases the expression of one or more NFκB-associated genes found to be decreased in the subject compared to a healthy control subject. Clause 25f. The method of any one of clauses 1 to 24, wherein the administration of Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof decreases the expression of one of more NFκB-associated genes in the subject and / or increases the expression of one of more NFκB-associated genes in the subject. Clause 26. The method of any one of clauses 25 to 25f, wherein Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof, decreases the expression of one or more NFκB-associated genes selected from: A4, ABCA1, ABCB1, ABCB4, ABCB9, ABCC6, ABCG5, ABCG8, ADAM19, ADH1A, ADORA1, ADORA2A, ADRA2B. AFP, AGER, AGT, AHCTF1, AICDA, AKR1C1, ALOX12, ALOX5, AMACR, AMH, ANGPT1, APOBEC2, APOC3, APOD, APOE, AQP4, AR, ARFRP1, ART1, ASPH, ASS1, ATP1A2, B2M, BACE1, BAX, BCL2, BCL2A1, BCL2L1, BCL2L11, BCL3, BDKRB1, BDKRB1, BDNF, BGN, BLIMP1 / PRDM1, BLNK, BLR1, BMI1, BMP2, BMP4, BNIP3, BRCA2, BTK, C3, C4A, C4BPA, C69, CALCB, CASP4, CAV1, CCL1, CCL15, CCL17, CCL19, CCL2, CCL20, CCL22, CCL23, CCL28, CCL3, CCL4, CCL5, CCND1, CCND2, CCND3, CCR5, CCR7, CD209, CD274, CD38, CD3G, CD40, CD40LG, CD44, CD48, CD54, CD80, CD83, CD86, CDK6, CDKN1A, CDX1, CEBPD, CFB, CFLAR, CGM3, CHI3L1, CIDEA, CLDN2, COL1A2, CR2, CREB3, CRP, CSF1, CSF2, CSF3, CTSB, CTSL1, CXCL1, CXCL10, CXCL11, CXCL3, CXCL5, CXCL6, CXCL9, CYP19A1, CYP27B1, CYP2C11, CYP2E1, CYP7B1, DCTN4, DEFB2, DIO2, DMP1, DNASE1L2, DPYD, DUSP1, E2F3, EBI3, EDN1, EGFR, EGR1, ELF3, ENG, ENO2, EPHA1, EPO, ERBB2, ERVWE1, F11R, F3, F8, FABP6, FAM148A, FAS, FASLG, FCER2. FCER2 / CD23, FCGRT, FGF8, FN1, FOS, FSTL3, FTH1, G6PC, G6PD, GAD1, GADD45B, GATA3, GBP1, GCLC, GCLM, GCNT1, GJB1, GNAI2, GNB2L1, GNRH2, GRIN1, GRIN2A, GRM2, GRO-beta, DB1 / 147901903.2 110 GRO-gamma, GSTP1, GUCY1A2, GZMB, HAMP, HAS1, HBE1, HBZ, HGF, HIF1A, HLA-B, HLA-G, HMGN1, HMOX1, HOXA9, HPSE, HSD11B2, HSD17B8, HSP90AA1, ICOS, IDO1, IER2, IER3, IFI44L, IFNB, IFNG, IGFBP1, IGFBP2, IGHE, IGHG1, IGHG2, IGHG4, IGKC, Iigp1, IL10, IL11, IL12A, IL12B, IL13, IL15, IL17, IL1A, IL1B, IL1RN, IL2, IL23A, IL27, IL2RA, IL6, IL8, IL8RA, IL8RB, IL9, INHBA, IRF1, IRF2, IRF4, IRF7, JMJD3, JUNB, KC, KCNK5, KCNN2, KISS1, KITLG, KLF10, KLK3, KLRA1, KRT15, KRT3, KRT5, KRT6B, LAMB2, LBP, LCN2, LEF1, LGALS3, LIPG, LTA, LTB, LTF, LYZ, MADCAM1, MAP4K1, MBP, MDK, MMP1, MMP3, MMP9, MT3, MTHFR, MUC2, MX1, MYB, MYC, MYLK, MYOZ1, NCAM, NFKB1, NFKB2, NFKBIA, NFKBIE, NFKBIZ, NGFB, NK4, NLRP2, NOD2, NOS1, NOS2A, NOX1, NPY1R, NQO1, NR3C1, NR4A2, NRG1, NUAK2, OLR1, OPN1SW, OPRD1, OPRM1, ORM1, Osterix, OXTR, PAFAH2, PAX8, PDE7A, PDGFB, PDYN, PENK, PGK1, PGLYRP1, PGR, PI3KAP1, PIGF, pIgR, PIK3CA, PIM1, PLA2, PLAU, PLCD1, PLK3, POMC, PPARGC1B, PPP5C, PRF1, PRKACA, PRKCD, PRL, PSMB9, PSME1, PSME2, PTAFR,, PTEN, PTGDS, PTGES, PTGIS, PTGS2, PTHLH, PTPN1, PTPN13, PTS, PTX3, PYCARD, RAG1, RAG2, RBBP4, Rdh1, Rdh7, REL, RELB, REV3L, RIPK2, S100A10, S100A4, S100A6, SAA1, SAA2, SAA, SAT1, SCNN1A, SDC4, SELE, SELP, SELS, SENP2, SERPINA1, SERPINA2, SERPINA3, SERPINB1, SERPINE1, PAI-1, SERPINE2, SH3BGRL, SKALP, PI3, SKP2, SLC11A2, SLC16A1, SLC3A2, SLC6A6, Slfn2, SNAI1, SOD1, SOD2, SOX9, SPATA19, SPI1, SPP1, ST6GAL1, ST8SIA1, STAT5A, SUPV3L1, TACR1, TAP1, TAPBP, TCRB, TERT, TF, TFEC, TFF3, TFPI2, TGM1, TGM2, THBS1, THBS2, TICAM1, TIFA, TLR2, TLR9, TNC, TN, TNFAIP2, TNFAIP3, TNFRSF1B, TNFRSF4, TNFRSF9, TNFSF10, TNFSF13B, TNFSF13B, TNFSF15, TNIP1, TNIP3, TP53, TRAF1, TRAF2, TREM1, TRPC1, TWIST1, UBE2M, UCP2, UGCGL1, UPK1B, UPP1, VCAM1, VEGFC, VIM, VPS53, WNT10B, WT1, XDH, XIAP, YY1, and ZNF366. Clause 26a. The method of any one of clauses 25 to 26, wherein Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, decreases the expression of one or more NFκB-associated genes selected from: A4, ABCA1, ABCB1, ABCB4, ABCB9, ABCC6, ABCG5, ABCG8, ADAM19, ADH1A, ADORA1, ADORA2A, ADRA2B. AFP, AGER, AGT, AHCTF1, AICDA, AKR1C1, ALOX12, ALOX5, AMACR, AMH, ANGPT1, APOBEC2, APOC3, APOD, APOE, AQP4, AR, ARFRP1, ART1, ASPH, ASS1, ATP1A2, B2M, BACE1, BAX, BCL2, BCL2A1, BCL2L1, BCL2L11, BCL3, BDKRB1, BDKRB1, DB1 / 147901903.2 111 BDNF, BGN, BLIMP1 / PRDM1, BLNK, BLR1, BMI1, BMP2, BMP4, BNIP3, BRCA2, BTK, C3, C4A, C4BPA, C69, CALCB, CASP4, CAV1, CCL1, CCL15, CCL17, CCL19, CCL2, CCL20, CCL22, CCL23, CCL28, CCL3, CCL4, CCL5, CCND1, CCND2, CCND3, CCR5, CCR7, CD209, CD274, CD38, CD3G, CD40, CD40LG, CD44, CD48, CD54, CD80, CD83, CD86, CDK6, CDKN1A, CDX1, CEBPD, CFB, CFLAR, CGM3, CHI3L1, CIDEA, CLDN2, COL1A2, CR2, CREB3, CRP, CSF1, CSF2, CSF3, CTSB, CTSL1, CXCL1, CXCL10, CXCL11, CXCL3, CXCL5, CXCL6, CXCL9, CYP19A1, CYP27B1, CYP2C11, CYP2E1, CYP7B1, DCTN4, DEFB2, DIO2, DMP1, DNASE1L2, DPYD, DUSP1, E2F3, EBI3, EDN1, EGFR, EGR1, ELF3, ENG, ENO2, EPHA1, EPO, ERBB2, ERVWE1, F11R, F3, F8, FABP6, FAM148A, FAS, FASLG, FCER2. FCER2 / CD23, FCGRT, FGF8, FN1, FOS, FSTL3, FTH1, G6PC, G6PD, GAD1, GADD45B, GATA3, GBP1, GCLC, GCLM, GCNT1, GJB1, GNAI2, GNB2L1, GNRH2, GRIN1, GRIN2A, GRM2, GRO-beta, GRO-gamma, GSTP1, GUCY1A2, GZMB, HAMP, HAS1, HBE1, HBZ, HGF, HIF1A, HLA-B, HLA-G, HMGN1, HMOX1, HOXA9, HPSE, HSD11B2, HSD17B8, HSP90AA1, ICOS, IDO1, IER2, IER3, IFI44L, IFNB, IFNG, IGFBP1, IGFBP2, IGHE, IGHG1, IGHG2, IGHG4, IGKC, Iigp1, IL10, IL11, IL12A, IL12B, IL13, IL15, IL17, IL1A, IL1B, IL1RN, IL2, IL23A, IL27, IL2RA, IL6, IL8, IL8RA, IL8RB, IL9, INHBA, IRF1, IRF2, IRF4, IRF7, JMJD3, JUNB, KC, KCNK5, KCNN2, KISS1, KITLG, KLF10, KLK3, KLRA1, KRT15, KRT3, KRT5, KRT6B, LAMB2, LBP, LCN2, LEF1, LGALS3, LIPG, LTA, LTB, LTF, LYZ, MADCAM1, MAP4K1, MBP, MDK, MMP1, MMP3, MMP9, MT3, MTHFR, MUC2, MX1, MYB, MYC, MYLK, MYOZ1, NCAM, NFKB1, NFKB2, NFKBIA, NFKBIE, NFKBIZ, NGFB, NK4, NLRP2, NOD2, NOS1, NOS2A, NOX1, NPY1R, NQO1, NR3C1, NR4A2, NRG1, NUAK2, OLR1, OPN1SW, OPRD1, OPRM1, ORM1, Osterix, OXTR, PAFAH2, PAX8, PDE7A, PDGFB, PDYN, PENK, PGK1, PGLYRP1, PGR, PI3KAP1, PIGF, pIgR, PIK3CA, PIM1, PLA2, PLAU, PLCD1, PLK3, POMC, PPARGC1B, PPP5C, PRF1, PRKACA, PRKCD, PRL, PSMB9, PSME1, PSME2, PTAFR,, PTEN, PTGDS, PTGES, PTGIS, PTGS2, PTHLH, PTPN1, PTPN13, PTS, PTX3, PYCARD, RAG1, RAG2, RBBP4, Rdh1, Rdh7, REL, RELB, REV3L, RIPK2, S100A10, S100A4, S100A6, SAA1, SAA2, SAA, SAT1, SCNN1A, SDC4, SELE, SELP, SELS, SENP2, SERPINA1, SERPINA2, SERPINA3, SERPINB1, SERPINE1, PAI-1, SERPINE2, SH3BGRL, SKALP, PI3, SKP2, SLC11A2, SLC16A1, SLC3A2, SLC6A6, Slfn2, SNAI1, SOD1, SOD2, SOX9, SPATA19, SPI1, SPP1, ST6GAL1, ST8SIA1, STAT5A, SUPV3L1, TACR1, TAP1, DB1 / 147901903.2 112 TAPBP, TCRB, TERT, TF, TFEC, TFF3, TFPI2, TGM1, TGM2, THBS1, THBS2, TICAM1, TIFA, TLR2, TLR9, TNC, TN, TNFAIP2, TNFAIP3, TNFRSF1B, TNFRSF4, TNFRSF9, TNFSF10, TNFSF13B, TNFSF13B, TNFSF15, TNIP1, TNIP3, TP53, TRAF1, TRAF2, TREM1, TRPC1, TWIST1, UBE2M, UCP2, UGCGL1, UPK1B, UPP1, VCAM1, VEGFC, VIM, VPS53, WNT10B, WT1, XDH, XIAP, YY1, and ZNF366. Clause 27. The method of any one of clauses 25 to 25f, 26, or 26a, wherein Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof, increases the expression of one or more NFκB-associated genes selected from: A4, ABCA1, ABCB1, ABCB4, ABCB9, ABCC6, ABCG5, ABCG8, ADAM19, ADH1A, ADORA1, ADORA2A, ADRA2B. AFP, AGER, AGT, AHCTF1, AICDA, AKR1C1, ALOX12, ALOX5, AMACR, AMH, ANGPT1, APOBEC2, APOC3, APOD, APOE, AQP4, AR, ARFRP1, ART1, ASPH, ASS1, ATP1A2, B2M, BACE1, BAX, BCL2, BCL2A1, BCL2L1, BCL2L11, BCL3, BDKRB1, BDKRB1, BDNF, BGN, BLIMP1 / PRDM1, BLNK, BLR1, BMI1, BMP2, BMP4, BNIP3, BRCA2, BTK, C3, C4A, C4BPA, C69, CALCB, CASP4, CAV1, CCL1, CCL15, CCL17, CCL19, CCL2, CCL20, CCL22, CCL23, CCL28, CCL3, CCL4, CCL5, CCND1, CCND2, CCND3, CCR5, CCR7, CD209, CD274, CD38, CD3G, CD40, CD40LG, CD44, CD48, CD54, CD80, CD83, CD86, CDK6, CDKN1A, CDX1, CEBPD, CFB, CFLAR, CGM3, CHI3L1, CIDEA, CLDN2, COL1A2, CR2, CREB3, CRP, CSF1, CSF2, CSF3, CTSB, CTSL1, CXCL1, CXCL10, CXCL11, CXCL3, CXCL5, CXCL6, CXCL9, CYP19A1, CYP27B1, CYP2C11, CYP2E1, CYP7B1, DCTN4, DEFB2, DIO2, DMP1, DNASE1L2, DPYD, DUSP1, E2F3, EBI3, EDN1, EGFR, EGR1, ELF3, ENG, ENO2, EPHA1, EPO, ERBB2, ERVWE1, F11R, F3, F8, FABP6, FAM148A, FAS, FASLG, FCER2. FCER2 / CD23, FCGRT, FGF8, FN1, FOS, FSTL3, FTH1, G6PC, G6PD, GAD1, GADD45B, GATA3, GBP1, GCLC, GCLM, GCNT1, GJB1, GNAI2, GNB2L1, GNRH2, GRIN1, GRIN2A, GRM2, GRO-beta, GRO-gamma, GSTP1, GUCY1A2, GZMB, HAMP, HAS1, HBE1, HBZ, HGF, HIF1A, HLA-B, HLA-G, HMGN1, HMOX1, HOXA9, HPSE, HSD11B2, HSD17B8, HSP90AA1, ICOS, IDO1, IER2, IER3, IFI44L, IFNB, IFNG, IGFBP1, IGFBP2, IGHE, IGHG1, IGHG2, IGHG4, IGKC, Iigp1, IL10, IL11, IL12A, IL12B, IL13, IL15, IL17, IL1A, IL1B, IL1RN, IL2, IL23A, IL27, IL2RA, IL6, IL8, IL8RA, IL8RB, DB1 / 147901903.2 113 IL9, INHBA, IRF1, IRF2, IRF4, IRF7, JMJD3, JUNB, KC, KCNK5, KCNN2, KISS1, KITLG, KLF10, KLK3, KLRA1, KRT15, KRT3, KRT5, KRT6B, LAMB2, LBP, LCN2, LEF1, LGALS3, LIPG, LTA, LTB, LTF, LYZ, MADCAM1, MAP4K1, MBP, MDK, MMP1, MMP3, MMP9, MT3, MTHFR, MUC2, MX1, MYB, MYC, MYLK, MYOZ1, NCAM, NFKB1, NFKB2, NFKBIA, NFKBIE, NFKBIZ, NGFB, NK4, NLRP2, NOD2, NOS1, NOS2A, NOX1, NPY1R, NQO1, NR3C1, NR4A2, NRG1, NUAK2, OLR1, OPN1SW, OPRD1, OPRM1, ORM1, Osterix, OXTR, PAFAH2, PAX8, PDE7A, PDGFB, PDYN, PENK, PGK1, PGLYRP1, PGR, PI3KAP1, PIGF, pIgR, PIK3CA, PIM1, PLA2, PLAU, PLCD1, PLK3, POMC, PPARGC1B, PPP5C, PRF1, PRKACA, PRKCD, PRL, PSMB9, PSME1, PSME2, PTAFR,, PTEN, PTGDS, PTGES, PTGIS, PTGS2, PTHLH, PTPN1, PTPN13, PTS, PTX3, PYCARD, RAG1, RAG2, RBBP4, Rdh1, Rdh7, REL, RELB, REV3L, RIPK2, S100A10, S100A4, S100A6, SAA1, SAA2, SAA, SAT1, SCNN1A, SDC4, SELE, SELP, SELS, SENP2, SERPINA1, SERPINA2, SERPINA3, SERPINB1, SERPINE1, PAI-1, SERPINE2, SH3BGRL, SKALP, PI3, SKP2, SLC11A2, SLC16A1, SLC3A2, SLC6A6, Slfn2, SNAI1, SOD1, SOD2, SOX9, SPATA19, SPI1, SPP1, ST6GAL1, ST8SIA1, STAT5A, SUPV3L1, TACR1, TAP1, TAPBP, TCRB, TERT, TF, TFEC, TFF3, TFPI2, TGM1, TGM2, THBS1, THBS2, TICAM1, TIFA, TLR2, TLR9, TNC, TN, TNFAIP2, TNFAIP3, TNFRSF1B, TNFRSF4, TNFRSF9, TNFSF10, TNFSF13B, TNFSF13B, TNFSF15, TNIP1, TNIP3, TP53, TRAF1, TRAF2, TREM1, TRPC1, TWIST1, UBE2M, UCP2, UGCGL1, UPK1B, UPP1, VCAM1, VEGFC, VIM, VPS53, WNT10B, WT1, XDH, XIAP, YY1, and ZNF366. Clause 27a. The method of any one of clauses 25 to 25f, 26, 26a, or 27 wherein Compound 8, Compound 9, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, increases the expression of one or more NFκB-associated genes selected from: A4, ABCA1, ABCB1, ABCB4, ABCB9, ABCC6, ABCG5, ABCG8, ADAM19, ADH1A, ADORA1, ADORA2A, ADRA2B. AFP, AGER, AGT, AHCTF1, AICDA, AKR1C1, ALOX12, ALOX5, AMACR, AMH, ANGPT1, APOBEC2, APOC3, APOD, APOE, AQP4, AR, ARFRP1, ART1, ASPH, ASS1, ATP1A2, B2M, BACE1, BAX, BCL2, BCL2A1, BCL2L1, BCL2L11, BCL3, BDKRB1, BDKRB1, BDNF, BGN, BLIMP1 / PRDM1, BLNK, BLR1, BMI1, BMP2, BMP4, BNIP3, BRCA2, BTK, C3, C4A, C4BPA, C69, CALCB, CASP4, CAV1, CCL1, CCL15, CCL17, CCL19, CCL2, CCL20, CCL22, CCL23, CCL28, CCL3, CCL4, CCL5, CCND1, CCND2, CCND3, CCR5, CCR7, CD209, CD274, CD38, CD3G, CD40, CD40LG, CD44, CD48, DB1 / 147901903.2 114 CD54, CD80, CD83, CD86, CDK6, CDKN1A, CDX1, CEBPD, CFB, CFLAR, CGM3, CHI3L1, CIDEA, CLDN2, COL1A2, CR2, CREB3, CRP, CSF1, CSF2, CSF3, CTSB, CTSL1, CXCL1, CXCL10, CXCL11, CXCL3, CXCL5, CXCL6, CXCL9, CYP19A1, CYP27B1, CYP2C11, CYP2E1, CYP7B1, DCTN4, DEFB2, DIO2, DMP1, DNASE1L2, DPYD, DUSP1, E2F3, EBI3, EDN1, EGFR, EGR1, ELF3, ENG, ENO2, EPHA1, EPO, ERBB2, ERVWE1, F11R, F3, F8, FABP6, FAM148A, FAS, FASLG, FCER2. FCER2 / CD23, FCGRT, FGF8, FN1, FOS, FSTL3, FTH1, G6PC, G6PD, GAD1, GADD45B, GATA3, GBP1, GCLC, GCLM, GCNT1, GJB1, GNAI2, GNB2L1, GNRH2, GRIN1, GRIN2A, GRM2, GRO-beta, GRO- gamma, GSTP1, GUCY1A2, GZMB, HAMP, HAS1, HBE1, HBZ, HGF, HIF1A, HLA-B, HLA-G, HMGN1, HMOX1, HOXA9, HPSE, HSD11B2, HSD17B8, HSP90AA1, ICOS, IDO1, IER2, IER3, IFI44L, IFNB, IFNG, IGFBP1, IGFBP2, IGHE, IGHG1, IGHG2, IGHG4, IGKC, Iigp1, IL10, IL11, IL12A, IL12B, IL13, IL15, IL17, IL1A, IL1B, IL1RN, IL2, IL23A, IL27, IL2RA, IL6, IL8, IL8RA, IL8RB, IL9, INHBA, IRF1, IRF2, IRF4, IRF7, JMJD3, JUNB, KC, KCNK5, KCNN2, KISS1, KITLG, KLF10, KLK3, KLRA1, KRT15, KRT3, KRT5, KRT6B, LAMB2, LBP, LCN2, LEF1, LGALS3, LIPG, LTA, LTB, LTF, LYZ, MADCAM1, MAP4K1, MBP, MDK, MMP1, MMP3, MMP9, MT3, MTHFR, MUC2, MX1, MYB, MYC, MYLK, MYOZ1, NCAM, NFKB1, NFKB2, NFKBIA, NFKBIE, NFKBIZ, NGFB, NK4, NLRP2, NOD2, NOS1, NOS2A, NOX1, NPY1R, NQO1, NR3C1, NR4A2, NRG1, NUAK2, OLR1, OPN1SW, OPRD1, OPRM1, ORM1, Osterix, OXTR, PAFAH2, PAX8, PDE7A, PDGFB, PDYN, PENK, PGK1, PGLYRP1, PGR, PI3KAP1, PIGF, pIgR, PIK3CA, PIM1, PLA2, PLAU, PLCD1, PLK3, POMC, PPARGC1B, PPP5C, PRF1, PRKACA, PRKCD, PRL, PSMB9, PSME1, PSME2, PTAFR,, PTEN, PTGDS, PTGES, PTGIS, PTGS2, PTHLH, PTPN1, PTPN13, PTS, PTX3, PYCARD, RAG1, RAG2, RBBP4, Rdh1, Rdh7, REL, RELB, REV3L, RIPK2, S100A10, S100A4, S100A6, SAA1, SAA2, SAA, SAT1, SCNN1A, SDC4, SELE, SELP, SELS, SENP2, SERPINA1, SERPINA2, SERPINA3, SERPINB1, SERPINE1, PAI-1, SERPINE2, SH3BGRL, SKALP, PI3, SKP2, SLC11A2, SLC16A1, SLC3A2, SLC6A6, Slfn2, SNAI1, SOD1, SOD2, SOX9, SPATA19, SPI1, SPP1, ST6GAL1, ST8SIA1, STAT5A, SUPV3L1, TACR1, TAP1, TAPBP, TCRB, TERT, TF, TFEC, TFF3, TFPI2, TGM1, TGM2, THBS1, THBS2, TICAM1, TIFA, TLR2, TLR9, TNC, TN, TNFAIP2, TNFAIP3, TNFRSF1B, TNFRSF4, TNFRSF9, TNFSF10, TNFSF13B, TNFSF13B, TNFSF15, TNIP1, TNIP3, TP53, DB1 / 147901903.2 115 TRAF1, TRAF2, TREM1, TRPC1, TWIST1, UBE2M, UCP2, UGCGL1, UPK1B, UPP1, VCAM1, VEGFC, VIM, VPS53, WNT10B, WT1, XDH, XIAP, YY1, and ZNF366. Clause 27b. The method of any one of clauses 1 to 27a, wherein the subject in need thereof has elevated secretion of one or more cytokines, optionally wherein the one or more cytokines are selected from: TNF-α, IL-1 β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, IL-23, GM- CSF, and IFN-γ. Clause 27c. The method of clause 27b, wherein the subject in need thereof has elevated secretion of one or more cytokines compared to a healthy control subject, optionally wherein the one or more cytokines are selected from: TNF-α, IL-1 β, IL-2, IL-4, IL-5, IL-6, IL- 10, IL-12, IL-13, IL-17, IL-23, GM-CSF, and IFN-γ. Clause 27d. The method of any one of clauses 27a to 27c, wherein Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof, decreases the secretion of one or more cytokines found to be elevated in the subject, optionally wherein the compound decreases the secretion of one or more cytokines selected from: TNF-α, IL-1 β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, IL-23, GM-CSF, and IFN-γ in the subject. Clause 27e. The method of any one of clauses 27a to 27e, wherein Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, decreases the secretion of one or more cytokines found to be elevated in the subject, optionally wherein the compound decreases the secretion of one or more cytokines selected from: TNF-α, IL-1 β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, IL-23, GM-CSF, and IFN-γ in the subject. Clause 27f. The method of clause 27e, wherein the administration of Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof, decreases the expression of the one or more cytokines found to be elevated in the subject before the administration of Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one DB1 / 147901903.2 116 thereof, and / or increases the expression of the one or more cytokines found to be decreased in the subject before the administration of Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof. Clause 27g. The method of clause 27e or 27f, wherein the administration of Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, decreases the expression of the one or more cytokines found to be elevated in the subject before the administration of Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, and / or increases the expression of the one or more cytokines found to be decreased in the subject before the administration of Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof. Clause 27h. The method of any one of clauses 27e to 27g, wherein upon administration to the subject, Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof, decreases the expression of one or more cytokines found to be elevated in the subject compared to a healthy control subject, and / or increases the expression of one or more cytokines found to be decreased in the subject compared to a healthy control subject. Clause 27i. The method of any one of clauses 27e to 27h, wherein upon administration to the subject, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, decreases the expression of one or more cytokines found to be elevated in the subject compared to a healthy control subject, and / or increases the expression of one or more cytokines found to be decreased in the subject compared to a healthy control subject. Clause 27j. The method of any one of clauses 27 to 27i, wherein upon administration to the subject, Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, decreases the expression of one or more cytokines in the subject, and / or DB1 / 147901903.2 117 increases the expression of one or more cytokines in the subject compared to a healthy control subject. Clause 28. The method of any one of clauses 1 to 27j, wherein Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof, is more effective at inhibiting cancer cell colony formation and / or cancer progenitor cell function when compared to a compound which inhibits IRAK1 without inhibiting IRAK4 or inhibits IRAK4 without inhibiting IRAK1. Clause 28a. The method of any one of clauses 1 to 27i or 28, Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, is more effective at inhibiting cancer cell colony formation and / or cancer progenitor cell function when compared to a compound which inhibits IRAK1 without inhibiting IRAK4 or inhibits IRAK4 without inhibiting IRAK1. Clause 29. The method of any one of clauses 1 to 28a, wherein Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof, provides sustained treatment of the inflammatory disease / disorder, AML, or MDS in the subject. Clause 29a. The method of any one of clauses 1 to 29, wherein Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, provides sustained treatment of the inflammatory disease / disorder, AML, or MDS in the subject. Clause 30. The method of clause 29 or 29a, wherein the sustained treatment is greater than the treatment provided from a compound which inhibits IRAK1 without inhibiting IRAK4 or inhibits IRAK4 without inhibiting IRAK1. Clause 31. The method of any one of clauses 1 to 30, wherein Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof, continues to treat the inflammatory disease / disorder, AML, or MDS in the subject after the administration is stopped. Clause 31a. The method of any DB1 / 147901903.2 118 one of clauses 1 to 31, wherein Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof, continues to treat the inflammatory disease / disorder, AML, or MDS in the subject after the administration is stopped. Clause 32. The method of clause 31 or 31a, wherein Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof, continues to treat the inflammatory disease / disorder, AML, or MDS in the subject for about 1 day, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, about one week, about two weeks, about three weeks, or about a month after the administration is stopped. Clause 32a. The method of clause 31, wherein Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, continues to treat the inflammatory disease / disorder, AML, or MDS in the subject for about 1 day, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, about one week, about two weeks, about three weeks, or about a month after the administration is stopped. Clause 33. The method of any one of clauses 1 to 32a, wherein the administration comprises parenteral administration, a mucosal administration, intravenous administration, subcutaneous administration, topical administration, intradermal administration, oral administration, sublingual administration, intranasal administration, or intramuscular administration. Clause 34. The method of any one of clauses 1 to 33, wherein Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof, is administered to the subject in an amount of from about 0.005 mg / kg subject body weight to about 1,000 mg / kg subject body weight or in a dosage of from about 0.35 mg to about 70,000 mg. Clause 34a. The method of any one of clauses 1 to 34, wherein Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, is administered to the subject in an amount of from about 0.005 mg / kg subject body weight to about 1,000 mg / kg subject body weight or in a dosage of from about 0.35 mg to about 70,000 mg. DB1 / 147901903.2 119 Clause 35. The method of any one of clauses 1 to 34a, wherein Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof, is used in combination with one or more of: a chemotherapy agent, a BCL2 inhibitor, an immune modulator, a BTK inhibitor, a DNA methyltransferase inhibitor / hypomethylating agent, an anthracycline, a histone deacetylase (HDAC) inhibitor, a purine nucleoside analogue (antimetabolite), an isocitrate dehydrogenase 1 or 2 (IDH1 and / or IDH2) inhibitor, an antibody-drug conjugate, an mAbs / immunotherapy, a Plk inhibitor, a MEK inhibitor, a CDK inhibitor, a CDK9 inhibitor, a CDK8 inhibitor, a retinoic acid receptor agonist, a TP53 activator, a CELMoD, a smoothened receptor antagonist, an ERK inhibitor including an ERK2 / MAPK1 or ERK1 / MAPK3 inhibitor, a PI3K inhibitor, an mTOR inhibitor, a steroid or glucocorticoid, a steroid or glucocorticoid receptor modulator, an EZH2 inhibitor, a hedgehog (Hh) inhibitor, a Topoisomerase I inhibitor, a Topoisomerase II inhibitor, an aminopeptidase / Leukotriene A4 hydrolase inhibitor, a FLT3 / Axl / ALK inhibitor, a FLT3 / KIT / PDGFR, PKC, and / or KDR inhibitor, a Syk inhibitor, an E-selectin inhibitor, an NEDD8-activator, an MDM2 inhibitor, a PLK1 inhibitor, an Aura A inhibitor, an aurora kinase inhibitor, an EGFR inhibitor, an AuroraB / C / VEGFR1 / 2 / 3 / FLT3 / CSF-1R / Kit / PDGFRA / B inhibitor, an AKT 1, 2, and / or 3 inhibitor, a ABL1 / 2 / SRC / EPHA2 / LCK / YES1 / KIT / PDGFRB / FYN inhibitor, a farnesyltransferase inhibitor, a BRAF / MAP2K1 / MAP2K2 inhibitor, a Menin-KMT2A / MLL inhibitor, and a multikinase inhibitor. Clause 35a. The method of any one of clauses 1 to 35, wherein Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, is used in combination with one or more of: a chemotherapy agent, a BCL2 inhibitor, an immune modulator, a BTK inhibitor, a DNA methyltransferase inhibitor / hypomethylating agent, an anthracycline, a histone deacetylase (HDAC) inhibitor, a purine nucleoside analogue (antimetabolite), an isocitrate dehydrogenase 1 or 2 (IDH1 and / or IDH2) inhibitor, an antibody- drug conjugate, an mAbs / immunotherapy, a Plk inhibitor, a MEK inhibitor, a CDK inhibitor, a CDK9 inhibitor, a CDK8 inhibitor, a retinoic acid receptor agonist, a TP53 activator, a CELMoD, a smoothened receptor antagonist, an ERK inhibitor including an ERK2 / MAPK1 or ERK1 / MAPK3 inhibitor, a PI3K inhibitor, an mTOR inhibitor, a steroid or glucocorticoid, a DB1 / 147901903.2 120 steroid or glucocorticoid receptor modulator, an EZH2 inhibitor, a hedgehog (Hh) inhibitor, a Topoisomerase I inhibitor, a Topoisomerase II inhibitor, an aminopeptidase / Leukotriene A4 hydrolase inhibitor, a FLT3 / Axl / ALK inhibitor, a FLT3 / KIT / PDGFR, PKC, and / or KDR inhibitor, a Syk inhibitor, an E-selectin inhibitor, an NEDD8-activator, an MDM2 inhibitor, a PLK1 inhibitor, an Aura A inhibitor, an aurora kinase inhibitor, an EGFR inhibitor, an AuroraB / C / VEGFR1 / 2 / 3 / FLT3 / CSF-1R / Kit / PDGFRA / B inhibitor, an AKT 1, 2, and / or 3 inhibitor, a ABL1 / 2 / SRC / EPHA2 / LCK / YES1 / KIT / PDGFRB / FYN inhibitor, a farnesyltransferase inhibitor, a BRAF / MAP2K1 / MAP2K2 inhibitor, a Menin-KMT2A / MLL inhibitor, and a multikinase inhibitor. Clause 36. The method of clause 35 or 35a, wherein Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof, is used in combination with at least one of a BCL2 inhibitor, a BTK inhibitor, a glucocorticoid, a CDK inhibitor, and a DNA methyltransferase inhibitor. Clause 36a. The method of any one of clauses 35, 35a, or 36 wherein Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, is used in combination with at least one of a BCL2 inhibitor, a BTK inhibitor, a glucocorticoid, a CDK inhibitor, and a DNA methyltransferase inhibitor. Clause 37. The method of any one of clauses 35, 35a, 36, or 36a, wherein the BCL2 inhibitor is venetoclax or a pharmaceutically acceptable salt thereof. Clause 38. The method of clause 37, wherein the combination of Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof, and venetoclax, or a pharmaceutically acceptable salt thereof, increases survival of the subject. Clause 38a. The method of clause 37 or 38, wherein the combination of Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, and venetoclax, or a pharmaceutically acceptable salt thereof, increases survival of the subject. DB1 / 147901903.2 121 Clause 39. The method of clause 38 or 38a, wherein the combination of Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof, and venetoclax, or a pharmaceutically acceptable salt thereof, and venetoclax, or a pharmaceutically acceptable salt thereof, increases survival of the subject compared to a subject administered either Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof, and venetoclax, or a pharmaceutically acceptable salt thereof, or venetoclax, or a pharmaceutically acceptable salt thereof. Clause 39a. The method of any one of clauses 38, 38a, or 39, wherein the combination of Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, and venetoclax, or a pharmaceutically acceptable salt thereof, increases survival of the subject compared to a subject administered either Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, or venetoclax, or a pharmaceutically acceptable salt thereof. Clause 40. The method of clause 39 or 39a, wherein the combination of Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof, and venetoclax, or a pharmaceutically acceptable salt thereof, and venetoclax, or a pharmaceutically acceptable salt thereof, increases survival of the subject by about 10% to 200%, about 10% to 175%, about 20% to 175%, or about 20% to 150% compared to the subject administered either Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, Compound 13, Compound 14, Compound 15, CA-4948 (Emavusertib), R835, R289, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer of any one thereof, and venetoclax, or a pharmaceutically acceptable salt ther...

Claims

CLAIMS 1. A method of treating an inflammatory disease or disorder, or a cancer selected from acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), in a subject in need thereof, the method comprising administering to the subject Compound 8: or a salt, ester, solvate, optical of an isomer thereof.

2. The method of claim 1, wherein the inflammatory disease or disorder is selected from chronic inflammation, sepsis, rheumatoid arthritis, hidradenitis suppurativa, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, psoriasis, Sjögren’s syndrome, Ankylosing spondylitis, systemic sclerosis, Type 1 diabetes mellitus, Crohn’s disease, atopic dermatitis, and colitis.

3. The method of claim 1, wherein: the AML is relapsed AML, refractory AML, relapsed / refractory AML, AML with resistance to hypomethylating agents, AML with resistance to venetoclax, AML with resistance to hypomethylating agents and venetoclax, monocytic AML, or monocytic-like AML, or the MDS is MDS with a mutation in isocitrate dehydrogenase 1, MDS with a mutation in isocitrate dehydrogenase 2, or MDS with a splicing factor mutation, optionally wherein the MDS with a splicing factor mutation comprises MDS with a splicing factor mutation in U2AF1, SRSF2, SF3B1, or ZRSR2.

4. The method of claim 1 or 3, wherein: the subject has AML and the subject has a gene mutation in one or more of FLT3, TET2, KIT, BCOR, BRAF, CDKN2A, UTX, ZRSR2, NPM1, PTEN, DNMT3A, EZH2, RUNX1, DB1 / 147901903.2 317JAK2, ASXL1, ABL1, ATRX, BCORL1, KDM6A, PTPN11, TP53, CBL, CEBPA, FBXW7, HRAS, NRAS, IDH1, IDH2, NRAS, PDGFRA, SF3B1, ETV6, PHF6, GNAS, KRAS, NOTCH1, STAG2, SETBP1, GATA1, GATA2, WT1, SRSF2, GNAS, CEBPA, CALR, MPL, BCL11A, ATM, CTCF, U2AF1, TYK2, FBX, RUI, RAD21, or MLL3, or the subject has MDS and the subject has a gene mutation in one or more of U2AF1, FLT3, ASXL1, BCORL1, BRAF, CBL, CDKN2A, DNMT3A, FBXW7, GATA2, IDH2, KRAS, NOTCH1, NRAS, PDGFRA, PTEN, PTPN11, TET2, TP53, EZH2, HRAS, KIT, MPL, PHF6, RUNX1, WT1, ABL1, CEBPA, ETV6, IDH2, KDM6A, KIT, KRAS, PTEN, RUNX1, SF3B1, or ZRSR2.

5. The method of any one of claims 1 to 4, wherein Compound 8 has an IRAK1 IC50 of less than about 40 nM, optionally less than about 5 nM, and / or a FLT3 IC50 of less than about 2.5 nM.

6. The method of any one of claims 1 to 5, wherein Compound 8 has an IRAK4:IRAK1 inhibitory potency ratio of less than about 40.

7. The method of any one of claims 1 to 6, wherein the subject in need thereof has elevated expression of one or more IRAK1 / 4-associated genes and / or decreased expression of one or more IRAK1 / 4-associated genes.

8. The method of claim 7, wherein the subject in need thereof has elevated expression and / or decreased expression of one or more IRAK1 / 4-associated genes compared to a healthy control subject.

9. The method of claim 7 or 8, wherein the subject in need thereof has elevated expression of one or more IRAK1 / 4-associated genes selected from: PLS3, HSBP1L1, CDC42BPA, PPP2R3A, GNG12, PENK, STC2, DNAJC22, SH3D19, GABRD, RAVER2, ARHGEF26, APBB2, BAI2, DPEP1, LGI2, PIP5K1A, SOX18, BMP4, TMC4, KCNIP3, CCNO, ULK4P2, FAM57A, SCARA3, CERS1, BEND5, HAPLN3, DNMBP, KIAA1522, PIR, GTF3C5 ECHDC3, ICAM1, RAB3A, SDHA, C9orf116, MKI67, LMTK3, MCM10, ADM2, DB1 / 147901903.2 318HSD17B14, LOC102724002, KCNH2, PRAME, KIAA1279, LOC101929974, ARHGAP21, SULT2B1, ADCY6, GBF1, TUBGCP2, CD19, SPIRE2, SH3PXD2B, AADAT, FOXC1, ZBED3, TSKU, NRARP, AMIGO2, PCBD1, TCAM1P, FAM57B, LOC101929021, PCK2, CCDC127, MGMT, C6orf147, TGFB1I1, DPP4, ALX4, TACC2, WLS, PACSIN3, NAPA-AS1, LINC00999, BAIAP3, ANKH, VDAC2, TAF3, ECHS1, EFNA3, CORO6, TCTN2, HPS1, DNAJB12, SPIB, SLC29A3, PHGDH, PTMS, TMEM91, SEC24C, HGD, MSS51, TEAD3, LARP4B, ZCCHC24, ARHGEF16, FOXO6, FBXO18, PPRC1, CCDC78, RHBDL1, SPINT1, STON2, NUDT8, NEBL, EPAS1, FAM178A, PI4K2A, SNED1, STAM, PLOD2, TM7SF2, FGD1, PCDHB6, CCNB3, MCMDC2, EDRF1, NRM, PPIF, ATF5, BRD9, B3GALT4, NET1, TMEM169, RPH3AL, DROSHA, RBMS2, POLR3A, TRIP13, LPHN1, ZMIZ1, RP11-344B5.2, HNRNPF, HSD17B7P2, SLIT1, LOC648987, ACTR1A, CCT5, S1PR5, WDFY4, GRK5, SREBF1, STXBP5L, VARS2, GAB2, ZFP36L1, CPNE7, HSPA2, NAT8L, DOK4, IGF1R, KHK, KIRREL2, COMTD1, ZNF488, CASC10, QRICH2, RBM17, LSS, PAX8, PKN3, HELLS, FN3K, CDC42EP1, NFIX, BMS1, STOX1, SEMA4B, SUPV3L1, FAM198A, RCOR2, PDCD, PPAP2A, DDX12P, ACY3, TSPAN10, NUP155, RIBC2, PLCXD1, TP53INP2, GOLPH3, WDR70, BTRC, SVIL, DTX4, DUSP5, ECE1, MRPL43, SKP2, SNHG3, MYRF, ZFYVE27, H2AFY2, NOLC1, SLC25A28, WNK2, NDUFS6, SLC30A3, LOC642846, NEURL1B, ARMC4, SFXN3, VASH2, NOTUM, VCL, LOC100506901, CSTF2T, PRICKLE1, ZNF132, GPR153, ZMYND11, DGCR5, OXER1, VTI1A, PCDHGC3, MORC4, EIF3A, PDCD11, SLC38A1, MC1R, CBS, AC002454.1, PDCD6, B4GALNT1, RPP38, SUGT1P1, NEDD4L, PROCA1, SH3PXD2A, JAG2, FGFR3, TMEM191B, SEPHS1, LOC100505761, C21orf58, FADS1, TET1, GBGT1, KAT6B, KIFC2, TAF5, CASP7, PELI3, PP7080, ATN1, KIAA1598, FAM115A, NKX3-2, CHCHD10, GPSM1, LRP4, CDT1, EIF4EBP2, AASS, ABCC6P1, ABCD2, ADAMTS14, AGAP4, AGAP9, AIFM2, AKR1C1, AKR1E2, ANK3, ANKRD33B, ANO6, APBB1IP, ARHGAP19, ARNTL2, ARSG, ARTN, ASCC1, ASUN, BAG3, BEND4, BEX5, BLNK, BTAF1, C10orf10, C10orf12, C10orf76, C10orf91, C15orf38, C2CD4C, C2CD5, C3orf18, CALHM2, CAMK1D, CAPRIN2, CDH2, CDHR1, CEL, CEP72, CES3, CES4A, CHST3, CLIC5, CMAS, CNNM2, CNTN1, COL27A1, COL4A5, CPS1, CRABP1, CTBP2, CUEDC2, CXorf57, DAPK2, DDAH2, DDX11, DDX11-AS1, DENND5B, DHTKD1, DNM1L, DPCD, DPY19L2, DUSP5P1, EBF3, EFEMP2, EGFR, ELK1, EPHB4, FAM155B, FAM175B, FAM21C, FAM45A, FAM53B, FAM84B, FCER2, FGD4, FOXL2, DB1 / 147901903.2 319FZD8, GAS1, GPC6, GRIA3, GUCY1B3, GYPE, HDHD3, HES4, HIF1AN, HMGCS1, HMX2, HMX3, HOXB13, HOXB6, HSD17B8, HSH2D, IDE, INPP5A, INPP5F, INPP5J, IPO8, IRAK4, ITPR2, ITPR3, JMJD1C, KAZALD1, KCNQ5, KCNS3, KIAA1324, KIF11, KLHL42, KLLN, KRAS, KREMEN2, LAT, LDB1, LGALS3BP, LINC00477, LIPE, LOC100288152, LOC100506688, LOC100506691, LOC100507487, LOC101927104, LOC101927799, LOC101928913, LOC102723337, LOC102724472, LPCAT1, LRMP, LRRC10B, LRRC20, LRRC27, LTK, LY6G5C, LZTS2, MAP2K6, MASTL, MCIDAS, MCMBP, MDGA2, METTL12, METTL20, MMS19, MPPED2, MRPS16, MRPS35, MSX1, MX1, NDUFB8, NEURL1, NEUROG3, NFKB2, NIM1K, NKD2, NLGN2, NNT, NNT-AS1, NT5DC2, NUDT13, OGDHL, OVOL2, OXCT1, P2RX7, P4HA1, PABPC1L, PANK1, PAOX, PAPD7, PAPSS2, PCDHB13, PCDHB14, PCED1B, PCED1B-AS1, PCSK5, PDLIM1, PEAR1, PFKP, PGAM1, PGAM4, PI15, PITX1, PLEKHA8P1, PLEKHO1, PPFIBP1, PPP2R2D, PPP3CB, PRTFDC1, PSTPIP2, PTENP1, PVRL3, PWWP2B, PXDC1, RNF208, ROBO1, RP11- 184I16.4, RP11-53O19.1, RP11-96H19.1, RPAP3, RTN1, SAMD11, SAMD8, SCAF11, SCD5, SDHAP3, SEC14L2, SEC31B, SEC61A2, SECTM1, SFMBT2, SFXN2, SHANK3, SHISA3, SHISA7, SIDT1, SKIDA1, SLA2, SLC12A7, SLC16A6, SLC16A9, SLC4A11, SLITRK5, SMAD1, SNHG12, SNORA61, SNORD104, SOX1, SPEF2, SRRM3, SUFU, TARS, TCF7, TEX15, TGFBR3L, THBD, TIAL1, TLX3, TM7SF3, TMEM180, TMEM191C, TMEM255A, TMEM63C, TRIM72, TUBB3, TYSND1, UGT3A2, ULK2, UNC13D, USP54, VENTX, VIM, XPNPEP1, YARS2, YPEL3, ZDHHC16, ZDHHC6, ZNF43, ZNF438, ZNF503, ZNF503-AS2, ZNF511, ZNF574, ZNF622, ZNF726, ZNF99, ZWINT, ADM, ALDOC, BNIP3, CA3, CD209, CSMD3, DDIT4, FCGR2B, FCGR2C, FIGN, GLIS2, SHISA8, SOX5, TBC1D30, TLE6, TLX1, VAT1L, VEGFA, ANXA4, APLN, C1QL4, CCDC102A, CHDH, EGLN3, ENO2, FADS2, HK2, HSPA7, IL17RB, KLF2, LAMC, LINC00263, LOC101928092, LOC102724908, MIR210HG, NRTN, PFKFB4, SCD, SLC4A3, SLC6A8, ZNF215, and ZNF395, optionally wherein the subject in need thereof has elevated expression of one or more IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, DB1 / 147901903.2 320PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3.

10. The method of claim 7 or 8, wherein the subject in need thereof has decreased expression of one or more IRAK1 / 4-associated genes selected from: PLS3, HSBP1L1, CDC42BPA, PPP2R3A, GNG12, PENK, STC2, DNAJC22, SH3D19, GABRD, RAVER2, ARHGEF26, APBB2, BAI2, DPEP1, LGI2, PIP5K1A, SOX18, BMP4, TMC4, KCNIP3, CCNO, ULK4P2, FAM57A, SCARA3, CERS1, BEND5, HAPLN3, DNMBP, KIAA1522, PIR, GTF3C5 ECHDC3, ICAM1, RAB3A, SDHA, C9orf116, MKI67, LMTK3, MCM10, ADM2, HSD17B14, LOC102724002, KCNH2, PRAME, KIAA1279, LOC101929974, ARHGAP21, SULT2B1, ADCY6, GBF1, TUBGCP2, CD19, SPIRE2, SH3PXD2B, AADAT, FOXC1, ZBED3, TSKU, NRARP, AMIGO2, PCBD1, TCAM1P, FAM57B, LOC101929021, PCK2, CCDC127, MGMT, C6orf147, TGFB1I1, DPP4, ALX4, TACC2, WLS, PACSIN3, NAPA-AS1, LINC00999, BAIAP3, ANKH, VDAC2, TAF3, ECHS1, EFNA3, CORO6, TCTN2, HPS1, DNAJB12, SPIB, SLC29A3, PHGDH, PTMS, TMEM91, SEC24C, HGD, MSS51, TEAD3, LARP4B, ZCCHC24, ARHGEF16, FOXO6, FBXO18, PPRC1, CCDC78, RHBDL1, SPINT1, STON2, NUDT8, NEBL, EPAS1, FAM178A, PI4K2A, SNED1, STAM, PLOD2, TM7SF2, FGD1, PCDHB6, CCNB3, MCMDC2, EDRF1, NRM, PPIF, ATF5, BRD9, B3GALT4, NET1, TMEM169, RPH3AL, DROSHA, RBMS2, POLR3A, TRIP13, LPHN1, ZMIZ1, RP11-344B5.2, HNRNPF, HSD17B7P2, SLIT1, LOC648987, ACTR1A, CCT5, S1PR5, WDFY4, GRK5, SREBF1, STXBP5L, VARS2, GAB2, ZFP36L1, CPNE7, HSPA2, NAT8L, DOK4, IGF1R, KHK, KIRREL2, COMTD1, ZNF488, CASC10, QRICH2, RBM17, LSS, PAX8, PKN3, HELLS, FN3K, CDC42EP1, NFIX, BMS1, STOX1, SEMA4B, SUPV3L1, FAM198A, RCOR2, PDCD4, PPAP2A, DDX12P, ACY3, TSPAN10, NUP155, RIBC2, PLCXD1, TP53INP2, GOLPH3, WDR70, BTRC, SVIL, DTX4, DUSP5, ECE1, MRPL43, SKP2, SNHG3, MYRF, ZFYVE27, H2AFY2, NOLC1, SLC25A28, WNK2, NDUFS6, SLC30A3, LOC642846, NEURL1B, ARMC4, SFXN3, VASH2, NOTUM, VCL, LOC100506901, CSTF2T, PRICKLE1, ZNF132, GPR153, ZMYND11, DGCR5, OXER1, VTI1A, PCDHGC3, MORC4, EIF3A, PDCD11, SLC38A1, MC1R, CBS, AC002454.1, PDCD6, B4GALNT1, RPP38, SUGT1P1, NEDD4L, PROCA1, SH3PXD2A, JAG2, FGFR3, TMEM191B, SEPHS1, LOC100505761, C21orf58, FADS1, TET1, GBGT1, KAT6B, KIFC2, TAF5, CASP7, PELI3, PP7080, ATN1, DB1 / 147901903.2 321KIAA1598, FAM115A, NKX3-2, CHCHD10, GPSM1, LRP4, CDT1, EIF4EBP2, AASS, ABCC6P1, ABCD2, ADAMTS14, AGAP4, AGAP9, AIFM2, AKR1C1, AKR1E2, ANK3, ANKRD33B, ANO6, APBB1IP, ARHGAP19, ARNTL2, ARSG, ARTN, ASCC1, ASUN, BAG3, BEND4, BEX5, BLNK, BTAF1, C10orf10, C10orf12, C10orf76, C10orf91, C15orf38, C2CD4C, C2CD5, C3orf18, CALHM2, CAMK1D, CAPRIN2, CDH2, CDHR1, CEL, CEP72, CES3, CES4A, CHST3, CLIC5, CMAS, CNNM2, CNTN1, COL27A1, COL4A5, CPS1, CRABP1, CTBP2, CUEDC2, CXorf57, DAPK2, DDAH2, DDX11, DDX11-AS1, DENND5B, DHTKD1, DNM1L, DPCD, DPY19L2, DUSP5P1, EBF3, EFEMP2, EGFR, ELK1, EPHB4, FAM155B, FAM175B, FAM21C, FAM45A, FAM53B, FAM84B, FCER2, FGD4, FOXL2, FZD8, GAS1, GPC6, GRIA3, GUCY1B3, GYPE, HDHD3, HES4, HIF1AN, HMGCS1, HMX2, HMX3, HOXB13, HOXB6, HSD17B8, HSH2D, IDE, INPP5A, INPP5F, INPP5J, IPO8, IRAK4, ITPR2, ITPR3, JMJD1C, KAZALD1, KCNQ5, KCNS3, KIAA1324, KIF11, KLHL42, KLLN, KRAS, KREMEN2, LAT, LDB1, LGALS3BP, LINC00477, LIPE, LOC100288152, LOC100506688, LOC100506691, LOC100507487, LOC101927104, LOC101927799, LOC101928913, LOC102723337, LOC102724472, LPCAT1, LRMP, LRRC10B, LRRC20, LRRC27, LTK, LY6G5C, LZTS2, MAP2K6, MASTL, MCIDAS, MCMBP, MDGA2, METTL12, METTL20, MMS19, MPPED2, MRPS16, MRPS35, MSX1, MX1, NDUFB8, NEURL1, NEUROG3, NFKB2, NIM1K, NKD2, NLGN2, NNT, NNT-AS1, NT5DC2, NUDT13, OGDHL, OVOL2, OXCT1, P2RX7, P4HA1, PABPC1L, PANK1, PAOX, PAPD7, PAPSS2, PCDHB13, PCDHB14, PCED1B, PCED1B-AS1, PCSK5, PDLIM1, PEAR1, PFKP, PGAM1, PGAM4, PI15, PITX1, PLEKHA8P1, PLEKHO1, PPFIBP1, PPP2R2D, PPP3CB, PRTFDC1, PSTPIP2, PTENP1, PVRL3, PWWP2B, PXDC1, RNF208, ROBO1, RP11- 184I16.4, RP11-53O19.1, RP11-96H19.1, RPAP3, RTN1, SAMD11, SAMD8, SCAF11, SCD5, SDHAP3, SEC14L2, SEC31B, SEC61A2, SECTM1, SFMBT2, SFXN2, SHANK3, SHISA3, SHISA7, SIDT1, SKIDA1, SLA2, SLC12A7, SLC16A6, SLC16A9, SLC4A11, SLITRK5, SMAD1, SNHG12, SNORA61, SNORD104, SOX1, SPEF2, SRRM3, SUFU, TARS, TCF7, TEX15, TGFBR3L, THBD, TIAL1, TLX3, TM7SF3, TMEM180, TMEM191C, TMEM255A, TMEM63C, TRIM72, TUBB3, TYSND1, UGT3A2, ULK2, UNC13D, USP54, VENTX, VIM, XPNPEP1, YARS2, YPEL3, ZDHHC16, ZDHHC6, ZNF43, ZNF438, ZNF503, ZNF503-AS2, ZNF511, ZNF574, ZNF622, ZNF726, ZNF99, ZWINT, ADM, ALDOC, BNIP3, CA3, CD209, CSMD3, DDIT4, FCGR2B, FCGR2C, FIGN, GLIS2, SHISA8, SOX5, TBC1D30, TLE6, TLX1, DB1 / 147901903.2 322VAT1L, VEGFA, ANXA4, APLN, C1QL4, CCDC102A, CHDH, EGLN3, ENO2, FADS2, HK2, HSPA7, IL17RB, KLF2, LAMC, LINC00263, LOC101928092, LOC102724908, MIR210HG, NRTN, PFKFB4, SCD, SLC4A3, SLC6A8, ZNF215, and ZNF395, optionally wherein the subject in need thereof has decreased expression of one or more IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3.

11. The method of any one of claims 1 to 10, wherein upon administration to the subject, Compound 8 decreases the expression of one or more IRAK1 / 4-associated genes in the subject, and / or increases the expression of one or more IRAK1 / 4-associated genes in the subject.

12. The method of any one of claims 1 to 10, wherein upon administration to the subject, Compound 8 decreases the expression of one or more IRAK1 / 4-associated genes found to be elevated in the subject, and / or increases the expression of one or more IRAK1 / 4-associated genes found to be decreased in the subject.

13. The method of claim 12, wherein the administration of Compound 8 decreases the expression of the one or more IRAK1 / 4-associated genes found to be elevated in the subject before the administration of Compound 8, and / or increases the expression of the one or more IRAK1 / 4-associated genes found to be decreased in the subject before the administration of Compound 8.

14. The method of any one of claims 11 to 13, wherein administration of Compound 8 decreases the expression of one or more IRAK1 / 4-associated genes found to be elevated in the subject compared to a healthy control subject, and / or increases the expression of one or more IRAK1 / 4-associated genes found to be decreased in the subject compared to a healthy control subject. DB1 / 147901903.2 32315. The method of any one of claims 11 to 14, wherein upon administration to the subject, Compound 8 decreases the expression of one or more IRAK1 / 4-associated genes selected from: PLS3, HSBP1L1, CDC42BPA, PPP2R3A, GNG12, PENK, STC2, DNAJC22, SH3D19, GABRD, RAVER2, ARHGEF26, APBB2, BAI2, DPEP1, LGI2, PIP5K1A, SOX18, BMP4, TMC4, KCNIP3, CCNO, ULK4P2, FAM57A, SCARA3, CERS1, BEND5, HAPLN3, DNMBP, KIAA1522, PIR, GTF3C5 ECHDC3, ICAM1, RAB3A, SDHA, C9orf116, MKI67, LMTK3, MCM10, ADM2, HSD17B14, LOC102724002, KCNH2, PRAME, KIAA1279, LOC101929974, ARHGAP21, SULT2B1, ADCY6, GBF1, TUBGCP2, CD19, SPIRE2, SH3PXD2B, AADAT, FOXC1, ZBED3, TSKU, NRARP, AMIGO2, PCBD1, TCAM1P, FAM57B, LOC101929021, PCK2, CCDC127, MGMT, C6orf147, TGFB1I1, DPP4, ALX4, TACC2, WLS, PACSIN3, NAPA-AS1, LINC00999, BAIAP3, ANKH, VDAC2, TAF3, ECHS1, EFNA3, CORO6, TCTN2, HPS1, DNAJB12, SPIB, SLC29A3, PHGDH, PTMS, TMEM91, SEC24C, HGD, MSS51, TEAD3, LARP4B, ZCCHC24, ARHGEF16, FOXO6, FBXO18, PPRC1, CCDC78, RHBDL1, SPINT1, STON2, NUDT8, NEBL, EPAS1, FAM178A, PI4K2A, SNED1, STAM, PLOD2, TM7SF2, FGD1, PCDHB6, CCNB3, MCMDC2, EDRF1, NRM, PPIF, ATF5, BRD9, B3GALT4, NET1, TMEM169, RPH3AL, DROSHA, RBMS2, POLR3A, TRIP13, LPHN1, ZMIZ1, RP11-344B5.2, HNRNPF, HSD17B7P2, SLIT1, LOC648987, ACTR1A, CCT5, S1PR5, WDFY4, GRK5, SREBF1, STXBP5L, VARS2, GAB2, ZFP36L1, CPNE7, HSPA2, NAT8L, DOK4, IGF1R, KHK, KIRREL2, COMTD1, ZNF488, CASC10, QRICH2, RBM17, LSS, PAX8, PKN3, HELLS, FN3K, CDC42EP1, NFIX, BMS1, STOX1, SEMA4B, SUPV3L1, FAM198A, RCOR2, PDCD4, PPAP2A, DDX12P, ACY3, TSPAN10, NUP155, RIBC2, PLCXD1, TP53INP2, GOLPH3, WDR70, BTRC, SVIL, DTX4, DUSP5, ECE1, MRPL43, SKP2, SNHG3, MYRF, ZFYVE27, H2AFY2, NOLC1, SLC25A28, WNK2, NDUFS6, SLC30A3, LOC642846, NEURL1B, ARMC4, SFXN3, VASH2, NOTUM, VCL, LOC100506901, CSTF2T, PRICKLE1, ZNF132, GPR153, ZMYND11, DGCR5, OXER1, VTI1A, PCDHGC3, MORC4, EIF3A, PDCD11, SLC38A1, MC1R, CBS, AC002454.1, PDCD6, B4GALNT1, RPP38, SUGT1P1, NEDD4L, PROCA1, SH3PXD2A, JAG2, FGFR3, TMEM191B, SEPHS1, LOC100505761, C21orf58, FADS1, TET1, GBGT1, KAT6B, KIFC2, TAF5, CASP7, PELI3, PP7080, ATN1, KIAA1598, FAM115A, NKX3-2, CHCHD10, GPSM1, LRP4, CDT1, EIF4EBP2, AASS, ABCC6P1, ABCD2, ADAMTS14, AGAP4, AGAP9, AIFM2, DB1 / 147901903.2 324AKR1C1, AKR1E2, ANK3, ANKRD33B, ANO6, APBB1IP, ARHGAP19, ARNTL2, ARSG, ARTN, ASCC1, ASUN, BAG3, BEND4, BEX5, BLNK, BTAF1, C10orf10, C10orf12, C10orf76, C10orf91, C15orf38, C2CD4C, C2CD5, C3orf18, CALHM2, CAMK1D, CAPRIN2, CDH2, CDHR1, CEL, CEP72, CES3, CES4A, CHST3, CLIC5, CMAS, CNNM2, CNTN1, COL27A1, COL4A5, CPS1, CRABP1, CTBP2, CUEDC2, CXorf57, DAPK2, DDAH2, DDX11, DDX11-AS1, DENND5B, DHTKD1, DNM1L, DPCD, DPY19L2, DUSP5P1, EBF3, EFEMP2, EGFR, ELK1, EPHB4, FAM155B, FAM175B, FAM21C, FAM45A, FAM53B, FAM84B, FCER2, FGD4, FOXL2, FZD8, GAS1, GPC6, GRIA3, GUCY1B3, GYPE, HDHD3, HES4, HIF1AN, HMGCS1, HMX2, HMX3, HOXB13, HOXB6, HSD17B8, HSH2D, IDE, INPP5A, INPP5F, INPP5J, IPO8, IRAK4, ITPR2, ITPR3, JMJD1C, KAZALD1, KCNQ5, KCNS3, KIAA1324, KIF11, KLHL42, KLLN, KRAS, KREMEN2, LAT, LDB1, LGALS3BP, LINC00477, LIPE, LOC100288152, LOC100506688, LOC100506691, LOC100507487, LOC101927104, LOC101927799, LOC101928913, LOC102723337, LOC102724472, LPCAT1, LRMP, LRRC10B, LRRC20, LRRC27, LTK, LY6G5C, LZTS2, MAP2K6, MASTL, MCIDAS, MCMBP, MDGA2, METTL12, METTL20, MMS19, MPPED2, MRPS16, MRPS35, MSX1, MX1, NDUFB8, NEURL1, NEUROG3, NFKB2, NIM1K, NKD2, NLGN2, NNT, NNT-AS1, NT5DC2, NUDT13, OGDHL, OVOL2, OXCT1, P2RX7, P4HA1, PABPC1L, PANK1, PAOX, PAPD7, PAPSS2, PCDHB13, PCDHB14, PCED1B, PCED1B-AS1, PCSK5, PDLIM1, PEAR1, PFKP, PGAM1, PGAM4, PI15, PITX1, PLEKHA8P1, PLEKHO1, PPFIBP1, PPP2R2D, PPP3CB, PRTFDC1, PSTPIP2, PTENP1, PVRL3, PWWP2B, PXDC1, RNF208, ROBO1, RP11-184I16.4, RP11-53O19.1, RP11-96H19.1, RPAP3, RTN1, SAMD11, SAMD8, SCAF11, SCD5, SDHAP3, SEC14L2, SEC31B, SEC61A2, SECTM1, SFMBT2, SFXN2, SHANK3, SHISA3, SHISA7, SIDT1, SKIDA1, SLA2, SLC12A7, SLC16A6, SLC16A9, SLC4A11, SLITRK5, SMAD1, SNHG12, SNORA61, SNORD104, SOX1, SPEF2, SRRM3, SUFU, TARS, TCF7, TEX15, TGFBR3L, THBD, TIAL1, TLX3, TM7SF3, TMEM180, TMEM191C, TMEM255A, TMEM63C, TRIM72, TUBB3, TYSND1, UGT3A2, ULK2, UNC13D, USP54, VENTX, VIM, XPNPEP1, YARS2, YPEL3, ZDHHC16, ZDHHC6, ZNF43, ZNF438, ZNF503, ZNF503-AS2, ZNF511, ZNF574, ZNF622, ZNF726, ZNF99, ZWINT, ADM, ALDOC, BNIP3, CA3, CD209, CSMD3, DDIT4, FCGR2B, FCGR2C, FIGN, GLIS2, SHISA8, SOX5, TBC1D30, TLE6, TLX1, VAT1L, VEGFA, ANXA4, APLN, C1QL4, CCDC102A, CHDH, EGLN3, ENO2, FADS2, HK2, HSPA, IL17RB, KLF2, LAMC, LINC00263, LOC101928092, DB1 / 147901903.2 325LOC102724908, MIR210HG, NRTN, PFKFB4, SCD, SLC4A3, SLC6A8, ZNF215, and ZNF395 in the subject, optionally wherein the compound decreases the expression of one or more IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3 in the subject.

16. The method of any one of claims 11 to 14, wherein upon administration to the subject, Compound 8 increases the expression of one or more IRAK1 / 4-associated genes selected from: PLS3, HSBP1L1, CDC42BPA, PPP2R3A, GNG12, PENK, STC2, DNAJC22, SH3D19, GABRD, RAVER2, ARHGEF26, APBB2, BAI2, DPEP1, LGI2, PIP5K1A, SOX18, BMP4, TMC4, KCNIP3, CCNO, ULK4P2, FAM57A, SCARA3, CERS1, BEND5, HAPLN3, DNMBP, KIAA1522, PIR, GTF3C5 ECHDC3, ICAM1, RAB3A, SDHA, C9orf116, MKI67, LMTK3, MCM10, ADM2, HSD17B14, LOC102724002, KCNH2, PRAME, KIAA1279, LOC101929974, ARHGAP21, SULT2B1, ADCY6, GBF1, TUBGCP2, CD19, SPIRE2, SH3PXD2B, AADAT, FOXC1, ZBED3, TSKU, NRARP, AMIGO2, PCBD1, TCAM1P, FAM57B, LOC101929021, PCK2, CCDC127, MGMT, C6orf147, TGFB1I1, DPP4, ALX4, TACC2, WLS, PACSIN3, NAPA-AS1, LINC00999, BAIAP3, ANKH, VDAC2, TAF3, ECHS1, EFNA3, CORO6, TCTN2, HPS1, DNAJB12, SPIB, SLC29A3, PHGDH, PTMS, TMEM91, SEC24C, HGD, MSS51, TEAD3, LARP4B, ZCCHC24, ARHGEF16, FOXO6, FBXO18, PPRC1, CCDC78, RHBDL1, SPINT1, STON2, NUDT8, NEBL, EPAS1, FAM178A, PI4K2A, SNED1, STAM, PLOD2, TM7SF2, FGD1, PCDHB6, CCNB3, MCMDC2, EDRF1, NRM, PPIF, ATF5, BRD9, B3GALT4, NET1, TMEM169, RPH3AL, DROSHA, RBMS2, POLR3A, TRIP13, LPHN1, ZMIZ1, RP11-344B5.2, HNRNPF, HSD17B7P2, SLIT1, LOC648987, ACTR1A, CCT5, S1PR5, WDFY4, GRK5, SREBF1, STXBP5L, VARS2, GAB2, ZFP36L1, CPNE7, HSPA2, NAT8L, DOK4, IGF1R, KHK, KIRREL2, COMTD1, ZNF488, CASC10, QRICH2, RBM17, LSS, PAX8, PKN3, HELLS, FN3K, CDC42EP1, NFIX, BMS1, STOX1, SEMA4B, SUPV3L1, FAM198A, RCOR2, PDCD4, PPAP2A, DDX12P, ACY3, TSPAN10, DB1 / 147901903.2 326NUP155, RIBC2, PLCXD1, TP53INP2, GOLPH3, WDR70, BTRC, SVIL, DTX4, DUSP5, ECE1, MRPL43, SKP2, SNHG3, MYRF, ZFYVE27, H2AFY2, NOLC1, SLC25A28, WNK2, NDUFS6, SLC30A3, LOC642846, NEURL1B, ARMC4, SFXN3, VASH2, NOTUM, VCL, LOC100506901, CSTF2T, PRICKLE1, ZNF132, GPR153, ZMYND11, DGCR5, OXER1, VTI1A, PCDHGC3, MORC4, EIF3A, PDCD11, SLC38A1, MC1R, CBS, AC002454.1, PDCD6, B4GALNT1, RPP38, SUGT1P1, NEDD4L, PROCA1, SH3PXD2A, JAG2, FGFR3, TMEM191B, SEPHS1, LOC100505761, C21orf58, FADS1, TET1, GBGT1, KAT6B, KIFC2, TAF5, CASP7, PELI3, PP7080, ATN1, KIAA1598, FAM115A, NKX3-2, CHCHD10, GPSM1, LRP4, CDT1, EIF4EBP2, AASS, ABCC6P1, ABCD2, ADAMTS14, AGAP4, AGAP9, AIFM2, AKR1C1, AKR1E2, ANK3, ANKRD33B, ANO6, APBB1IP, ARHGAP19, ARNTL2, ARSG, ARTN, ASCC1, ASUN, BAG3, BEND4, BEX5, BLNK, BTAF1, C10orf10, C10orf12, C10orf76, C10orf91, C15orf38, C2CD4C, C2CD5, C3orf18, CALHM2, CAMK1D, CAPRIN2, CDH2, CDHR1, CEL, CEP72, CES3, CES4A, CHST3, CLIC5, CMAS, CNNM2, CNTN1, COL27A1, COL4A5, CPS1, CRABP1, CTBP2, CUEDC2, CXorf57, DAPK2, DDAH2, DDX11, DDX11-AS1, DENND5B, DHTKD1, DNM1L, DPCD, DPY19L2, DUSP5P1, EBF3, EFEMP2, EGFR, ELK1, EPHB4, FAM155B, FAM175B, FAM21C, FAM45A, FAM53B, FAM84B, FCER2, FGD4, FOXL2, FZD8, GAS1, GPC6, GRIA3, GUCY1B3, GYPE, HDHD3, HES4, HIF1AN, HMGCS1, HMX2, HMX3, HOXB13, HOXB6, HSD17B8, HSH2D, IDE, INPP5A, INPP5F, INPP5J, IPO8, IRAK4, ITPR2, ITPR3, JMJD1C, KAZALD1, KCNQ5, KCNS3, KIAA1324, KIF11, KLHL42, KLLN, KRAS, KREMEN2, LAT, LDB1, LGALS3BP, LINC00477, LIPE, LOC100288152, LOC100506688, LOC100506691, LOC100507487, LOC101927104, LOC101927799, LOC101928913, LOC102723337, LOC102724472, LPCAT1, LRMP, LRRC10B, LRRC20, LRRC27, LTK, LY6G5C, LZTS2, MAP2K6, MASTL, MCIDAS, MCMBP, MDGA2, METTL12, METTL20, MMS19, MPPED2, MRPS16, MRPS35, MSX1, MX1, NDUFB8, NEURL1, NEUROG3, NFKB2, NIM1K, NKD2, NLGN2, NNT, NNT-AS1, NT5DC2, NUDT13, OGDHL, OVOL2, OXCT1, P2RX7, P4HA1, PABPC1L, PANK1, PAOX, PAPD7, PAPSS2, PCDHB13, PCDHB14, PCED1B, PCED1B-AS1, PCSK5, PDLIM1, PEAR1, PFKP, PGAM1, PGAM4, PI15, PITX1, PLEKHA8P1, PLEKHO1, PPFIBP1, PPP2R2D, PPP3CB, PRTFDC1, PSTPIP2, PTENP1, PVRL3, PWWP2B, PXDC1, RNF208, ROBO1, RP11-184I16.4, RP11-53O19.1, RP11-96H19.1, RPAP3, RTN1, SAMD11, SAMD8, SCAF11, SCD5, SDHAP3, SEC14L2, SEC31B, SEC61A2, SECTM1, SFMBT2, SFXN2, SHANK3, DB1 / 147901903.2 327SHISA3, SHISA7, SIDT1, SKIDA1, SLA2, SLC12A7, SLC16A6, SLC16A9, SLC4A11, SLITRK5, SMAD1, SNHG12, SNORA61, SNORD104, SOX1, SPEF2, SRRM3, SUFU, TARS, TCF7, TEX15, TGFBR3L, THBD, TIAL1, TLX3, TM7SF3, TMEM180, TMEM191C, TMEM255A, TMEM63C, TRIM72, TUBB3, TYSND1, UGT3A2, ULK2, UNC13D, USP54, VENTX, VIM, XPNPEP1, YARS2, YPEL3, ZDHHC16, ZDHHC6, ZNF43, ZNF438, ZNF503, ZNF503-AS2, ZNF511, ZNF574, ZNF622, ZNF726, ZNF99, ZWINT, ADM, ALDOC, BNIP3, CA3, CD209, CSMD3, DDIT4, FCGR2B, FCGR2C, FIGN, GLIS2, SHISA8, SOX5, TBC1D30, TLE6, TLX1, VAT1L, VEGFA, ANXA4, APLN, C1QL4, CCDC102A, CHDH, EGLN3, ENO2, FADS2, HK2, HSPA7, IL17RB, KLF2, LAMC, LINC00263, LOC101928092, LOC102724908, MIR210HG, NRTN, PFKFB4, SCD, SLC4A3, SLC6A8, ZNF215, and ZNF395 in the subject, optionally wherein the compound increases the expression of one or more IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3 in the subject.

17. The method of any one of claims 1 to 16, wherein the subject in need thereof has elevated expression of one or more NFκB-associated genes, and / or decreased expression of one or more NFκB-associated genes.

18. The method of claim 17, wherein the subject in need thereof has elevated expression of one or more NFκB-associated genes compared to a healthy control subject, and / or decreased expression of one or more NFκB-associated genes compared to a healthy control subject.

19. The method of claim 17 or 18, wherein the subject in need thereof has elevated expression of one or more NFκB-associated genes selected from: A4, ABCA1, ABCB1, ABCB4, ABCB9, ABCC6, ABCG5, ABCG8, ADAM19, ADH1A, ADORA1, ADORA2A, ADRA2B. AFP, AGER, AGT, AHCTF1, AICDA, AKR1C1, ALOX12, ALOX5, AMACR, AMH, DB1 / 147901903.2 328ANGPT1, APOBEC2, APOC3, APOD, APOE, AQP4, AR, ARFRP1, ART1, ASPH, ASS1, ATP1A2, B2M, BACE1, BAX, BCL2, BCL2A1, BCL2L1, BCL2L11, BCL3, BDKRB1, BDKRB1, BDNF, BGN, BLIMP1 / PRDM1, BLNK, BLR1, BMI1, BMP2, BMP4, BNIP3, BRCA2, BTK, C3, C4A, C4BPA, C69, CALCB, CASP4, CAV1, CCL1, CCL15, CCL17, CCL19, CCL2, CCL20, CCL22, CCL23, CCL28, CCL3, CCL4, CCL5, CCND1, CCND2, CCND3, CCR5, CCR7, CD209, CD274, CD38, CD3G, CD40, CD40LG, CD44, CD48, CD54, CD80, CD83, CD86, CDK6, CDKN1A, CDX1, CEBPD, CFB, CFLAR, CGM3, CHI3L1, CIDEA, CLDN2, COL1A2, CR2, CREB3, CRP, CSF1, CSF2, CSF3, CTSB, CTSL1, CXCL1, CXCL10, CXCL11, CXCL3, CXCL5, CXCL6, CXCL9, CYP19A1, CYP27B1, CYP2C11, CYP2E1, CYP7B1, DCTN4, DEFB2, DIO2, DMP1, DNASE1L2, DPYD, DUSP1, E2F3, EBI3, EDN1, EGFR, EGR1, ELF3, ENG, ENO2, EPHA1, EPO, ERBB2, ERVWE1, F11R, F3, F8, FABP6, FAM148A, FAS, FASLG, FCER2. FCER2 / CD23, FCGRT, FGF8, FN1, FOS, FSTL3, FTH1, G6PC, G6PD, GAD1, GADD45B, GATA3, GBP1, GCLC, GCLM, GCNT1, GJB1, GNAI2, GNB2L1, GNRH2, GRIN1, GRIN2A, GRM2, GRO-beta, GRO-gamma, GSTP1, GUCY1A2, GZMB, HAMP, HAS1, HBE1, HBZ, HGF, HIF1A, HLA-B, HLA-G, HMGN1, HMOX1, HOXA9, HPSE, HSD11B2, HSD17B8, HSP90AA1, ICOS, IDO1, IER2, IER3, IFI44L, IFNB, IFNG, IGFBP1, IGFBP2, IGHE, IGHG1, IGHG2, IGHG4, IGKC, Iigp1, IL10, IL11, IL12A, IL12B, IL13, IL15, IL17, IL1A, IL1B, IL1RN, IL2, IL23A, IL27, IL2RA, IL6, IL8, IL8RA, IL8RB, IL9, INHBA, IRF1, IRF2, IRF4, IRF7, JMJD3, JUNB, KC, KCNK5, KCNN2, KISS1, KITLG, KLF10, KLK3, KLRA1, KRT15, KRT3, KRT5, KRT6B, LAMB2, LBP, LCN2, LEF1, LGALS3, LIPG, LTA, LTB, LTF, LYZ, MADCAM1, MAP4K1, MBP, MDK, MMP1, MMP3, MMP9, MT3, MTHFR, MUC2, MX1, MYB, MYC, MYLK, MYOZ1, NCAM, NFKB1, NFKB2, NFKBIA, NFKBIE, NFKBIZ, NGFB, NK4, NLRP2, NOD2, NOS1, NOS2A, NOX1, NPY1R, NQO1, NR3C1, NR4A2, NRG1, NUAK2, OLR1, OPN1SW, OPRD1, OPRM1, ORM1, Osterix, OXTR, PAFAH2, PAX8, PDE7A, PDGFB, PDYN, PENK, PGK1, PGLYRP1, PGR, PI3KAP1, PIGF, pIgR, PIK3CA, PIM1, PLA2, PLAU, PLCD1, PLK3, POMC, PPARGC1B, PPP5C, PRF1, PRKACA, PRKCD, PRL, PSMB9, PSME1, PSME2, PTAFR,, PTEN, PTGDS, PTGES, PTGIS, PTGS2, PTHLH, PTPN1, PTPN13, PTS, PTX3, PYCARD, RAG1, RAG2, RBBP4, Rdh1, Rdh7, REL, RELB, REV3L, RIPK2, S100A10, S100A4, S100A6, SAA1, SAA2, SAA, SAT1, SCNN1A, SDC4, SELE, SELP, SELS, SENP2, SERPINA1, SERPINA2, SERPINA3, SERPINB1, SERPINE1, PAI-1, SERPINE2, SH3BGRL, DB1 / 147901903.2 329SKALP, PI3, SKP2, SLC11A2, SLC16A1, SLC3A2, SLC6A6, Slfn2, SNAI1, SOD1, SOD2, SOX9, SPATA19, SPI1, SPP1, ST6GAL1, ST8SIA1, STAT5A, SUPV3L1, TACR1, TAP1, TAPBP, TCRB, TERT, TF, TFEC, TFF3, TFPI2, TGM1, TGM2, THBS1, THBS2, TICAM1, TIFA, TLR2, TLR9, TNC, TN, TNFAIP2, TNFAIP3, TNFRSF1B, TNFRSF4, TNFRSF9, TNFSF10, TNFSF13B, TNFSF13B, TNFSF15, TNIP1, TNIP3, TP53, TRAF1, TRAF2, TREM1, TRPC1, TWIST1, UBE2M, UCP2, UGCGL1, UPK1B, UPP1, VCAM1, VEGFC, VIM, VPS53, WNT10B, WT1, XDH, XIAP, YY1, and ZNF366.

20. The method of claim 17 or 18, wherein the subject in need thereof has decreased expression of one or more NFκB-associated genes selected from: A4, ABCA1, ABCB1, ABCB4, ABCB9, ABCC6, ABCG5, ABCG8, ADAM19, ADH1A, ADORA1, ADORA2A, ADRA2B. AFP, AGER, AGT, AHCTF1, AICDA, AKR1C1, ALOX12, ALOX5, AMACR, AMH, ANGPT1, APOBEC2, APOC3, APOD, APOE, AQP4, AR, ARFRP1, ART1, ASPH, ASS1, ATP1A2, B2M, BACE1, BAX, BCL2, BCL2A1, BCL2L1, BCL2L11, BCL3, BDKRB1, BDKRB1, BDNF, BGN, BLIMP1 / PRDM1, BLNK, BLR1, BMI1, BMP2, BMP4, BNIP3, BRCA2, BTK, C3, C4A, C4BPA, C69, CALCB, CASP4, CAV1, CCL1, CCL15, CCL17, CCL19, CCL2, CCL20, CCL22, CCL23, CCL28, CCL3, CCL4, CCL5, CCND1, CCND2, CCND3, CCR5, CCR7, CD209, CD274, CD38, CD3G, CD40, CD40LG, CD44, CD48, CD54, CD80, CD83, CD86, CDK6, CDKN1A, CDX1, CEBPD, CFB, CFLAR, CGM3, CHI3L1, CIDEA, CLDN2, COL1A2, CR2, CREB3, CRP, CSF1, CSF2, CSF3, CTSB, CTSL1, CXCL1, CXCL10, CXCL11, CXCL3, CXCL5, CXCL6, CXCL9, CYP19A1, CYP27B1, CYP2C11, CYP2E1, CYP7B1, DCTN4, DEFB2, DIO2, DMP1, DNASE1L2, DPYD, DUSP1, E2F3, EBI3, EDN1, EGFR, EGR1, ELF3, ENG, ENO2, EPHA1, EPO, ERBB2, ERVWE1, F11R, F3, F8, FABP6, FAM148A, FAS, FASLG, FCER2. FCER2 / CD23, FCGRT, FGF8, FN1, FOS, FSTL3, FTH1, G6PC, G6PD, GAD1, GADD45B, GATA3, GBP1, GCLC, GCLM, GCNT1, GJB1, GNAI2, GNB2L1, GNRH2, GRIN1, GRIN2A, GRM2, GRO-beta, GRO-gamma, GSTP1, GUCY1A2, GZMB, HAMP, HAS1, HBE1, HBZ, HGF, HIF1A, HLA-B, HLA-G, HMGN1, HMOX1, HOXA9, HPSE, HSD11B2, HSD17B8, HSP90AA1, ICOS, IDO1, IER2, IER3, IFI44L, IFNB, IFNG, IGFBP1, IGFBP2, IGHE, IGHG1, IGHG2, IGHG4, IGKC, Iigp1, IL10, IL11, IL12A, IL12B, IL13, IL15, IL17, IL1A, IL1B, IL1RN, IL2, IL23A, IL27, IL2RA, IL6, IL8, IL8RA, IL8RB, IL9, INHBA, IRF1, IRF2, IRF4, IRF7, JMJD3, JUNB, KC, KCNK5, DB1 / 147901903.2 330KCNN2, KISS1, KITLG, KLF10, KLK3, KLRA1, KRT15, KRT3, KRT5, KRT6B, LAMB2, LBP, LCN2, LEF1, LGALS3, LIPG, LTA, LTB, LTF, LYZ, MADCAM1, MAP4K1, MBP, MDK, MMP1, MMP3, MMP9, MT3, MTHFR, MUC2, MX1, MYB, MYC, MYLK, MYOZ1, NCAM, NFKB1, NFKB2, NFKBIA, NFKBIE, NFKBIZ, NGFB, NK4, NLRP2, NOD2, NOS1, NOS2A, NOX1, NPY1R, NQO1, NR3C1, NR4A2, NRG1, NUAK2, OLR1, OPN1SW, OPRD1, OPRM1, ORM1, Osterix, OXTR, PAFAH2, PAX8, PDE7A, PDGFB, PDYN, PENK, PGK1, PGLYRP1, PGR, PI3KAP1, PIGF, pIgR, PIK3CA, PIM1, PLA2, PLAU, PLCD1, PLK3, POMC, PPARGC1B, PPP5C, PRF1, PRKACA, PRKCD, PRL, PSMB9, PSME1, PSME2, PTAFR,, PTEN, PTGDS, PTGES, PTGIS, PTGS2, PTHLH, PTPN1, PTPN13, PTS, PTX3, PYCARD, RAG1, RAG2, RBBP4, Rdh1, Rdh7, REL, RELB, REV3L, RIPK2, S100A10, S100A4, S100A6, SAA1, SAA2, SAA, SAT1, SCNN1A, SDC4, SELE, SELP, SELS, SENP2, SERPINA1, SERPINA2, SERPINA3, SERPINB1, SERPINE1, PAI-1, SERPINE2, SH3BGRL, SKALP, PI3, SKP2, SLC11A2, SLC16A1, SLC3A2, SLC6A6, Slfn2, SNAI1, SOD1, SOD2, SOX9, SPATA19, SPI1, SPP1, ST6GAL1, ST8SIA1, STAT5A, SUPV3L1, TACR1, TAP1, TAPBP, TCRB, TERT, TF, TFEC, TFF3, TFPI2, TGM1, TGM2, THBS1, THBS2, TICAM1, TIFA, TLR2, TLR9, TNC, TN, TNFAIP2, TNFAIP3, TNFRSF1B, TNFRSF4, TNFRSF9, TNFSF10, TNFSF13B, TNFSF13B, TNFSF15, TNIP1, TNIP3, TP53, TRAF1, TRAF2, TREM1, TRPC1, TWIST1, UBE2M, UCP2, UGCGL1, UPK1B, UPP1, VCAM1, VEGFC, VIM, VPS53, WNT10B, WT1, XDH, XIAP, YY1, and ZNF366.

21. The method of any one of claims 1 to 20, wherein upon administration to the subject, Compound 8 decreases the expression of one or more NFκB-associated genes in the subject, and / or increases the expression of one or more NFκB-associated genes in the subject.

22. The method of any one of claims 1 to 20, wherein upon administration to the subject, Compound 8 decreases the expression of one or more NFκB-associated genes found to be elevated in the subject, and / or increases the expression of one or more NFκB-associated genes found to be decreased in the subject.

23. The method of claim 21 or 22, wherein the administration of Compound 8 decreases the expression of the one or more NFκB-associated genes found to be elevated in the subject DB1 / 147901903.2 331before the administration of Compound 8, and / or increases the expression of the one or more NFκB-associated genes found to be decreased in the subject before the administration of Compound 8.

24. The method of any one of claims 21 to 23, wherein upon administration to the subject, Compound 8 decreases the expression of one or more NFκB-associated genes found to be elevated in the subject compared to a healthy control subject, and / or increases the expression of one or more NFκB-associated genes found to be decreased in the subject compared to a healthy control subject.

25. The method of any one of claims 21 to 24, wherein upon administration to the subject, Compound 8 decreases the expression of one or more NFκB-associated genes selected from: A4, ABCA1, ABCB1, ABCB4, ABCB9, ABCC6, ABCG5, ABCG8, ADAM19, ADH1A, ADORA1, ADORA2A, ADRA2B. AFP, AGER, AGT, AHCTF1, AICDA, AKR1C1, ALOX12, ALOX5, AMACR, AMH, ANGPT1, APOBEC2, APOC3, APOD, APOE, AQP4, AR, ARFRP1, ART1, ASPH, ASS1, ATP1A2, B2M, BACE1, BAX, BCL2, BCL2A1, BCL2L1, BCL2L11, BCL3, BDKRB1, BDKRB1, BDNF, BGN, BLIMP1 / PRDM1, BLNK, BLR1, BMI1, BMP2, BMP4, BNIP3, BRCA2, BTK, C3, C4A, C4BPA, C69, CALCB, CASP4, CAV1, CCL1, CCL15, CCL17, CCL19, CCL2, CCL20, CCL22, CCL23, CCL28, CCL3, CCL4, CCL5, CCND1, CCND2, CCND3, CCR5, CCR7, CD209, CD274, CD38, CD3G, CD40, CD40LG, CD44, CD48, CD54, CD80, CD83, CD86, CDK6, CDKN1A, CDX1, CEBPD, CFB, CFLAR, CGM3, CHI3L1, CIDEA, CLDN2, COL1A2, CR2, CREB3, CRP, CSF1, CSF2, CSF3, CTSB, CTSL1, CXCL1, CXCL10, CXCL11, CXCL3, CXCL5, CXCL6, CXCL9, CYP19A1, CYP27B1, CYP2C11, CYP2E1, CYP7B1, DCTN4, DEFB2, DIO2, DMP1, DNASE1L2, DPYD, DUSP1, E2F3, EBI3, EDN1, EGFR, EGR1, ELF3, ENG, ENO2, EPHA1, EPO, ERBB2, ERVWE1, F11R, F3, F8, FABP6, FAM148A, FAS, FASLG, FCER2. FCER2 / CD23, FCGRT, FGF8, FN1, FOS, FSTL3, FTH1, G6PC, G6PD, GAD1, GADD45B, GATA3, GBP1, GCLC, GCLM, GCNT1, GJB1, GNAI2, GNB2L1, GNRH2, GRIN1, GRIN2A, GRM2, GRO-beta, GRO-gamma, GSTP1, GUCY1A2, GZMB, HAMP, HAS1, HBE1, HBZ, HGF, HIF1A, HLA-B, HLA-G, HMGN1, HMOX1, HOXA9, HPSE, HSD11B2, HSD17B8, HSP90AA1, ICOS, IDO1, IER2, IER3, IFI44L, IFNB, IFNG, IGFBP1, IGFBP2, IGHE, IGHG1, IGHG2, IGHG4, IGKC, DB1 / 147901903.2 332Iigp1, IL10, IL11, IL12A, IL12B, IL13, IL15, IL17, IL1A, IL1B, IL1RN, IL2, IL23A, IL27, IL2RA, IL6, IL8, IL8RA, IL8RB, IL9, INHBA, IRF1, IRF2, IRF4, IRF7, JMJD3, JUNB, KC, KCNK5, KCNN2, KISS1, KITLG, KLF10, KLK3, KLRA1, KRT15, KRT3, KRT5, KRT6B, LAMB2, LBP, LCN2, LEF1, LGALS3, LIPG, LTA, LTB, LTF, LYZ, MADCAM1, MAP4K1, MBP, MDK, MMP1, MMP3, MMP9, MT3, MTHFR, MUC2, MX1, MYB, MYC, MYLK, MYOZ1, NCAM, NFKB1, NFKB2, NFKBIA, NFKBIE, NFKBIZ, NGFB, NK4, NLRP2, NOD2, NOS1, NOS2A, NOX1, NPY1R, NQO1, NR3C1, NR4A2, NRG1, NUAK2, OLR1, OPN1SW, OPRD1, OPRM1, ORM1, Osterix, OXTR, PAFAH2, PAX8, PDE7A, PDGFB, PDYN, PENK, PGK1, PGLYRP1, PGR, PI3KAP1, PIGF, pIgR, PIK3CA, PIM1, PLA2, PLAU, PLCD1, PLK3, POMC, PPARGC1B, PPP5C, PRF1, PRKACA, PRKCD, PRL, PSMB9, PSME1, PSME2, PTAFR,, PTEN, PTGDS, PTGES, PTGIS, PTGS2, PTHLH, PTPN1, PTPN13, PTS, PTX3, PYCARD, RAG1, RAG2, RBBP4, Rdh1, Rdh7, REL, RELB, REV3L, RIPK2, S100A10, S100A4, S100A6, SAA1, SAA2, SAA, SAT1, SCNN1A, SDC4, SELE, SELP, SELS, SENP2, SERPINA1, SERPINA2, SERPINA3, SERPINB1, SERPINE1, PAI-1, SERPINE2, SH3BGRL, SKALP, PI3, SKP2, SLC11A2, SLC16A1, SLC3A2, SLC6A6, Slfn2, SNAI1, SOD1, SOD2, SOX9, SPATA19, SPI1, SPP1, ST6GAL1, ST8SIA1, STAT5A, SUPV3L1, TACR1, TAP1, TAPBP, TCRB, TERT, TF, TFEC, TFF3, TFPI2, TGM1, TGM2, THBS1, THBS2, TICAM1, TIFA, TLR2, TLR9, TNC, TN, TNFAIP2, TNFAIP3, TNFRSF1B, TNFRSF4, TNFRSF9, TNFSF10, TNFSF13B, TNFSF13B, TNFSF15, TNIP1, TNIP3, TP53, TRAF1, TRAF2, TREM1, TRPC1, TWIST1, UBE2M, UCP2, UGCGL1, UPK1B, UPP1, VCAM1, VEGFC, VIM, VPS53, WNT10B, WT1, XDH, XIAP, YY1, and ZNF366 in the subject.

26. The method of any one of claims 21 to 24, wherein upon administration to the subject, Compound 8 increases the expression of one or more NFκB-associated genes selected from: A4, ABCA1, ABCB1, ABCB4, ABCB9, ABCC6, ABCG5, ABCG8, ADAM19, ADH1A, ADORA1, ADORA2A, ADRA2B. AFP, AGER, AGT, AHCTF1, AICDA, AKR1C1, ALOX12, ALOX5, AMACR, AMH, ANGPT1, APOBEC2, APOC3, APOD, APOE, AQP4, AR, ARFRP1, ART1, ASPH, ASS1, ATP1A2, B2M, BACE1, BAX, BCL2, BCL2A1, BCL2L1, BCL2L11, BCL3, BDKRB1, BDKRB1, BDNF, BGN, BLIMP1 / PRDM1, BLNK, BLR1, BMI1, BMP2, BMP4, BNIP3, BRCA2, BTK, C3, C4A, C4BPA, C69, CALCB, CASP4, CAV1, CCL1, DB1 / 147901903.2 333CCL15, CCL17, CCL19, CCL2, CCL20, CCL22, CCL23, CCL28, CCL3, CCL4, CCL5, CCND1, CCND2, CCND3, CCR5, CCR7, CD209, CD274, CD38, CD3G, CD40, CD40LG, CD44, CD48, CD54, CD80, CD83, CD86, CDK6, CDKN1A, CDX1, CEBPD, CFB, CFLAR, CGM3, CHI3L1, CIDEA, CLDN2, COL1A2, CR2, CREB3, CRP, CSF1, CSF2, CSF3, CTSB, CTSL1, CXCL1, CXCL10, CXCL11, CXCL3, CXCL5, CXCL6, CXCL9, CYP19A1, CYP27B1, CYP2C11, CYP2E1, CYP7B1, DCTN4, DEFB2, DIO2, DMP1, DNASE1L2, DPYD, DUSP1, E2F3, EBI3, EDN1, EGFR, EGR1, ELF3, ENG, ENO2, EPHA1, EPO, ERBB2, ERVWE1, F11R, F3, F8, FABP6, FAM148A, FAS, FASLG, FCER2. FCER2 / CD23, FCGRT, FGF8, FN1, FOS, FSTL3, FTH1, G6PC, G6PD, GAD1, GADD45B, GATA3, GBP1, GCLC, GCLM, GCNT1, GJB1, GNAI2, GNB2L1, GNRH2, GRIN1, GRIN2A, GRM2, GRO-beta, GRO-gamma, GSTP1, GUCY1A2, GZMB, HAMP, HAS1, HBE1, HBZ, HGF, HIF1A, HLA-B, HLA-G, HMGN1, HMOX1, HOXA9, HPSE, HSD11B2, HSD17B8, HSP90AA1, ICOS, IDO1, IER2, IER3, IFI44L, IFNB, IFNG, IGFBP1, IGFBP2, IGHE, IGHG1, IGHG2, IGHG4, IGKC, Iigp1, IL10, IL11, IL12A, IL12B, IL13, IL15, IL17, IL1A, IL1B, IL1RN, IL2, IL23A, IL27, IL2RA, IL6, IL8, IL8RA, IL8RB, IL9, INHBA, IRF1, IRF2, IRF4, IRF7, JMJD3, JUNB, KC, KCNK5, KCNN2, KISS1, KITLG, KLF10, KLK3, KLRA1, KRT15, KRT3, KRT5, KRT6B, LAMB2, LBP, LCN2, LEF1, LGALS3, LIPG, LTA, LTB, LTF, LYZ, MADCAM1, MAP4K1, MBP, MDK, MMP1, MMP3, MMP9, MT3, MTHFR, MUC2, MX1, MYB, MYC, MYLK, MYOZ1, NCAM, NFKB1, NFKB2, NFKBIA, NFKBIE, NFKBIZ, NGFB, NK4, NLRP2, NOD2, NOS1, NOS2A, NOX1, NPY1R, NQO1, NR3C1, NR4A2, NRG1, NUAK2, OLR1, OPN1SW, OPRD1, OPRM1, ORM1, Osterix, OXTR, PAFAH2, PAX8, PDE7A, PDGFB, PDYN, PENK, PGK1, PGLYRP1, PGR, PI3KAP1, PIGF, pIgR, PIK3CA, PIM1, PLA2, PLAU, PLCD1, PLK3, POMC, PPARGC1B, PPP5C, PRF1, PRKACA, PRKCD, PRL, PSMB9, PSME1, PSME2, PTAFR,, PTEN, PTGDS, PTGES, PTGIS, PTGS2, PTHLH, PTPN1, PTPN13, PTS, PTX3, PYCARD, RAG1, RAG2, RBBP4, Rdh1, Rdh7, REL, RELB, REV3L, RIPK2, S100A10, S100A4, S100A6, SAA1, SAA2, SAA, SAT1, SCNN1A, SDC4, SELE, SELP, SELS, SENP2, SERPINA1, SERPINA2, SERPINA3, SERPINB1, SERPINE1, PAI-1, SERPINE2, SH3BGRL, SKALP, PI3, SKP2, SLC11A2, SLC16A1, SLC3A2, SLC6A6, Slfn2, SNAI1, SOD1, SOD2, SOX9, SPATA19, SPI1, SPP1, ST6GAL1, ST8SIA1, STAT5A, SUPV3L1, TACR1, TAP1, TAPBP, TCRB, TERT, TF, TFEC, TFF3, TFPI2, TGM1, TGM2, THBS1, THBS2, TICAM1, TIFA, TLR2, TLR9, TNC, TN, TNFAIP2, TNFAIP3, TNFRSF1B, DB1 / 147901903.2 334TNFRSF4, TNFRSF9, TNFSF10, TNFSF13B, TNFSF13B, TNFSF15, TNIP1, TNIP3, TP53, TRAF1, TRAF2, TREM1, TRPC1, TWIST1, UBE2M, UCP2, UGCGL1, UPK1B, UPP1, VCAM1, VEGFC, VIM, VPS53, WNT10B, WT1, XDH, XIAP, YY1, and ZNF366 in the subject.

27. The method of any one of claims 1 to 26, wherein the subject in need thereof has elevated secretion of one or more cytokines, optionally wherein the one or more cytokines are selected from: TNF-α, IL-1 β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, IL-23, GM- CSF, and IFN-γ.

28. The method of claim 27, wherein the subject in need thereof has elevated secretion of one or more cytokines compared to a healthy control subject, optionally wherein the one or more cytokines are selected from: TNF-α, IL-1 β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, IL-23, GM-CSF, and IFN-γ.

29. The method of claim 27 or 28, wherein Compound 8 decreases the secretion of one or more cytokines in the subject, optionally wherein the compound decreases the secretion of one or more cytokines selected from: TNF-α, IL-1 β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL- 17, IL-23, GM-CSF, and IFN-γ in the subject.

30. The method of claim 27 or 28, wherein Compound 8 decreases the secretion of one or more cytokines found to be elevated in the subject, optionally wherein the compound decreases the secretion of one or more cytokines selected from: TNF-α, IL-1 β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, IL-23, GM-CSF, and IFN-γ in the subject.

31. The method of any one of claims 27 to 30, wherein the administration of Compound 8 decreases the expression of the one or more cytokines found to be elevated in the subject before the administration of Compound 8, and / or increases the expression of the one or more cytokines found to be decreased in the subject before the administration of Compound 8. DB1 / 147901903.2 33532. The method of any one of claims 27 to 31, wherein upon administration to the subject, Compound 8 decreases the expression of one or more cytokines found to be elevated in the subject compared to a healthy control subject, and / or increases the expression of one or more cytokines found to be decreased in the subject compared to a healthy control subject.

33. The method of any one of claims 1 to 32, wherein Compound 8 is more effective at inhibiting cancer cell colony formation and / or cancer progenitor cell function when compared to a compound which inhibits IRAK1 without inhibiting IRAK4 or inhibits IRAK4 without inhibiting IRAK1.

34. The method of any one of claims 1 to 33, wherein Compound 8 provides sustained treatment of the inflammatory disease or disorder, or the cancer selected from AML and MDS in the subject, optionally wherein the sustained treatment is greater than the treatment provided from a compound which inhibits IRAK1 without inhibiting IRAK4 or inhibits IRAK4 without inhibiting IRAK1.

35. The method of any one of claims 1 to 34, wherein: the administration comprises parenteral administration, mucosal administration, intravenous administration, subcutaneous administration, topical administration, intradermal administration, oral administration, sublingual administration, intranasal administration, or intramuscular administration; and / or Compound 8 is administered to the subject in an amount of from about 0.005 mg / kg subject body weight to about 1,000 mg / kg subject body weight; and / or Compound 8 is administered to the subject in a dosage of from about 0.35 mg to about 70,000 mg; and / or Compound 8 is administered to the subject daily, every other day, every third day, every fourth day, every fifth day, every sixth day, once a week, twice a month, or once a month.

36. The method of any one of claims 1 to 32, wherein Compound 8 treats the inflammatory disease or disorder, or the cancer selected from AML and MDS, in the subject during the time period that the compound is administered to the subject. DB1 / 147901903.2 33637. The method of any one of claims 1 to 36, wherein Compound 8 continues to treat the inflammatory disease or disorder, or the cancer selected from AML and MDS, in the subject after the administration is stopped, optionally wherein Compound 8 continues to treat the inflammatory disease or disorder, or the cancer selected from AML and MDS, in the subject for about 1 day, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, about one week, about two weeks, about three weeks, or about a month after the administration is stopped.

38. The method of any one of claims 1 to 37, further comprising administering to the subject one or more of: a chemotherapy agent, a BCL2 inhibitor, an immune modulator, a BTK inhibitor, a DNA methyltransferase inhibitor / hypomethylating agent, an anthracycline, a histone deacetylase (HDAC) inhibitor, a purine nucleoside analogue (antimetabolite), an isocitrate dehydrogenase 1 or 2 (IDH1 and / or IDH2) inhibitor, an antibody-drug conjugate, an mAbs / immunotherapy, a Plk inhibitor, a MEK inhibitor, a CDK inhibitor, a CDK9 inhibitor, a CDK8 inhibitor, a retinoic acid receptor agonist, a TP53 activator, a CELMoD, a smoothened receptor antagonist, an ERK inhibitor including an ERK2 / MAPK1 or ERK1 / MAPK3 inhibitor, a PI3K inhibitor, an mTOR inhibitor, a steroid or glucocorticoid, a steroid or glucocorticoid receptor modulator, an EZH2 inhibitor, a hedgehog (Hh) inhibitor, a Topoisomerase I inhibitor, a Topoisomerase II inhibitor, an aminopeptidase / Leukotriene A4 hydrolase inhibitor, a FLT3 / Axl / ALK inhibitor, a FLT3 / KIT / PDGFR, PKC, and / or KDR inhibitor, a Syk inhibitor, an E-selectin inhibitor, an NEDD8-activator, an MDM2 inhibitor, a PLK1 inhibitor, an Aura A inhibitor, an aurora kinase inhibitor, an EGFR inhibitor, an AuroraB / C / VEGFR1 / 2 / 3 / FLT3 / CSF- 1R / Kit / PDGFRA / B inhibitor, an AKT 1, 2, and / or 3 inhibitor, a ABL1 / 2 / SRC / EPHA2 / LCK / YES1 / KIT / PDGFRB / FYN inhibitor, a farnesyltransferase inhibitor, a BRAF / MAP2K1 / MAP2K2 inhibitor, a Menin-KMT2A / MLL inhibitor, and a multikinase inhibitor; optionally comprising administering to the subject at least one of a BCL2 inhibitor, a BTK inhibitor, a glucocorticoid, a CDK inhibitor, and a DNA methyltransferase inhibitor.

39. The method of claim 38, wherein: the BCL2 inhibitor is venetoclax or a pharmaceutically acceptable salt thereof; and / or DB1 / 147901903.2 337the BTK inhibitor is ibrutinib or a pharmaceutically acceptable salt thereof, or acalabrutinib or a pharmaceutically acceptable salt thereof; and / or the glucocorticoid is selected from dexamethasone, methylprednisolone, prednisolone or a pharmaceutically acceptable salt of any one thereof; and / or the CDK inhibitor is selected from CDK4 / 6 inhibitor Palbociclib, CDK7 inhibitor THZ1, and / or CDK9 inhibitors BAY1251152 and Atuveciclib, or a pharmaceutically acceptable salt of any one thereof; and / or the DNA methyltransferase inhibitor is azacitidine or a pharmaceutically acceptable salt thereof.

40. The method of claim 38 or 39, wherein the combination of Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, and venetoclax, or a pharmaceutically acceptable salt thereof, increases survival of the subject; optionally wherein the combination of Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, and venetoclax, or a pharmaceutically acceptable salt thereof, increases survival of the subject compared to a subject administered either Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, or venetoclax, or a pharmaceutically acceptable salt thereof; optionally wherein the combination of Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, and venetoclax, or a pharmaceutically acceptable salt thereof, increases survival of the subject by about 10% to 200%, about 10% to 175%, about 20% to 175%, or about 20% to 150% compared to the subject administered either Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, or venetoclax, or a pharmaceutically acceptable salt thereof.

41. A method of determining whether a subject with a disease or disorder selected from an inflammatory disease or disorder, and a cancer selected from acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), can be treated by administration of Compound 8 or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, the method comprising: determining whether the subject has an elevated expression of one or more IRAK1 / 4- associated genes and / or a decreased expression of one or more IRAK1 / 4-associated genes, DB1 / 147901903.2 338wherein the IRAK1 / 4-associated genes are selected from: PLS3, HSBP1L1, CDC42BPA, PPP2R3A, GNG12, PENK, STC2, DNAJC22, SH3D19, GABRD, RAVER2, ARHGEF26, APBB2, BAI2, DPEP1, LGI2, PIP5K1A, SOX18, BMP4, TMC4, KCNIP3, CCNO, ULK4P2, FAM57A, SCARA3, CERS1, BEND5, HAPLN3, DNMBP, KIAA1522, PIR, GTF3C5 ECHDC3, ICAM1, RAB3A, SDHA, C9orf116, MKI67, LMTK3, MCM10, ADM2, HSD17B14, LOC102724002, KCNH2, PRAME, KIAA1279, LOC101929974, ARHGAP21, SULT2B1, ADCY6, GBF1, TUBGCP2, CD19, SPIRE2, SH3PXD2B, AADAT, FOXC1, ZBED3, TSKU, NRARP, AMIGO2, PCBD1, TCAM1P, FAM57B, LOC101929021, PCK2, CCDC127, MGMT, C6orf147, TGFB1I1, DPP4, ALX4, TACC2, WLS, PACSIN3, NAPA-AS1, LINC00999, BAIAP3, ANKH, VDAC2, TAF3, ECHS1, EFNA3, CORO6, TCTN2, HPS1, DNAJB12, SPIB, SLC29A3, PHGDH, PTMS, TMEM91, SEC24C, HGD, MSS51, TEAD3, LARP4B, ZCCHC24, ARHGEF16, FOXO6, FBXO18, PPRC1, CCDC78, RHBDL1, SPINT1, STON2, NUDT8, NEBL, EPAS1, FAM178A, PI4K2A, SNED1, STAM, PLOD2, TM7SF2, FGD1, PCDHB6, CCNB3, MCMDC2, EDRF1, NRM, PPIF, ATF5, BRD9, B3GALT4, NET1, TMEM169, RPH3AL, DROSHA, RBMS2, POLR3A, TRIP13, LPHN1, ZMIZ1, RP11-344B5.2, HNRNPF, HSD17B7P2, SLIT1, LOC648987, ACTR1A, CCT5, S1PR5, WDFY4, GRK5, SREBF1, STXBP5L, VARS2, GAB2, ZFP36L1, CPNE7, HSPA2, NAT8L, DOK4, IGF1R, KHK, KIRREL2, COMTD1, ZNF488, CASC10, QRICH2, RBM17, LSS, PAX8, PKN3, HELLS, FN3K, CDC42EP1, NFIX, BMS1, STOX1, SEMA4B, SUPV3L1, FAM198A, RCOR2, PDCD4, PPAP2A, DDX12P, ACY3, TSPAN10, NUP155, RIBC2, PLCXD1, TP53INP2, GOLPH3, WDR70, BTRC, SVIL, DTX4, DUSP5, ECE1, MRPL43, SKP2, SNHG3, MYRF, ZFYVE27, H2AFY2, NOLC1, SLC25A28, WNK2, NDUFS6, SLC30A3, LOC642846, NEURL1B, ARMC4, SFXN3, VASH2, NOTUM, VCL, LOC100506901, CSTF2T, PRICKLE1, ZNF132, GPR153, ZMYND11, DGCR5, OXER1, VTI1A, PCDHGC3, MORC4, EIF3A, PDCD11, SLC38A1, MC1R, CBS, AC002454.1, PDCD6, B4GALNT1, RPP38, SUGT1P1, NEDD4L, PROCA1, SH3PXD2A, JAG2, FGFR3, TMEM191B, SEPHS1, LOC100505761, C21orf58, FADS1, TET1, GBGT1, KAT6B, KIFC2, TAF5, CASP7, PELI3, PP7080, ATN1, KIAA1598, FAM115A, NKX3-2, CHCHD10, GPSM1, LRP4, CDT1, EIF4EBP2, AASS, ABCC6P1, ABCD2, ADAMTS14, AGAP4, AGAP9, AIFM2, AKR1C1, AKR1E2, ANK3, ANKRD33B, ANO6, APBB1IP, ARHGAP19, ARNTL2, ARSG, ARTN, ASCC1, ASUN, BAG3, BEND4, BEX5, BLNK, BTAF1, C10orf10, C10orf12, C10orf76, C10orf91, C15orf38, C2CD4C, C2CD5, DB1 / 147901903.2 339C3orf18, CALHM2, CAMK1D, CAPRIN2, CDH2, CDHR1, CEL, CEP72, CES3, CES4A, CHST3, CLIC5, CMAS, CNNM2, CNTN1, COL27A1, COL4A5, CPS1, CRABP1, CTBP2, CUEDC2, CXorf57, DAPK2, DDAH2, DDX11, DDX11-AS1, DENND5B, DHTKD1, DNM1L, DPCD, DPY19L2, DUSP5P1, EBF3, EFEMP2, EGFR, ELK1, EPHB4, FAM155B, FAM175B, FAM21C, FAM45A, FAM53B, FAM84B, FCER2, FGD4, FOXL2, FZD8, GAS1, GPC6, GRIA3, GUCY1B3, GYPE, HDHD3, HES4, HIF1AN, HMGCS1, HMX2, HMX3, HOXB13, HOXB6, HSD17B8, HSH2D, IDE, INPP5A, INPP5F, INPP5J, IPO8, IRAK4, ITPR2, ITPR3, JMJD1C, KAZALD1, KCNQ5, KCNS3, KIAA1324, KIF11, KLHL42, KLLN, KRAS, KREMEN2, LAT, LDB1, LGALS3BP, LINC00477, LIPE, LOC100288152, LOC100506688, LOC100506691, LOC100507487, LOC101927104, LOC101927799, LOC101928913, LOC102723337, LOC102724472, LPCAT1, LRMP, LRRC10B, LRRC20, LRRC27, LTK, LY6G5C, LZTS2, MAP2K6, MASTL, MCIDAS, MCMBP, MDGA2, METTL12, METTL20, MMS19, MPPED2, MRPS16, MRPS35, MSX1, MX1, NDUFB8, NEURL1, NEUROG3, NFKB2, NIM1K, NKD2, NLGN2, NNT, NNT-AS1, NT5DC2, NUDT13, OGDHL, OVOL2, OXCT1, P2RX7, P4HA1, PABPC1L, PANK1, PAOX, PAPD7, PAPSS2, PCDHB13, PCDHB14, PCED1B, PCED1B-AS1, PCSK5, PDLIM1, PEAR1, PFKP, PGAM1, PGAM4, PI15, PITX1, PLEKHA8P1, PLEKHO1, PPFIBP1, PPP2R2D, PPP3CB, PRTFDC1, PSTPIP2, PTENP1, PVRL3, PWWP2B, PXDC1, RNF208, ROBO1, RP11-184I16.4, RP11-53O19.1, RP11-96H19.1, RPAP3, RTN1, SAMD11, SAMD8, SCAF11, SCD5, SDHAP3, SEC14L2, SEC31B, SEC61A2, SECTM1, SFMBT2, SFXN2, SHANK3, SHISA3, SHISA7, SIDT1, SKIDA1, SLA2, SLC12A7, SLC16A6, SLC16A9, SLC4A11, SLITRK5, SMAD1, SNHG12, SNORA61, SNORD104, SOX1, SPEF2, SRRM3, SUFU, TARS, TCF7, TEX15, TGFBR3L, THBD, TIAL1, TLX3, TM7SF3, TMEM180, TMEM191C, TMEM255A, TMEM63C, TRIM72, TUBB3, TYSND1, UGT3A2, ULK2, UNC13D, USP54, VENTX, VIM, XPNPEP1, YARS2, YPEL3, ZDHHC16, ZDHHC6, ZNF43, ZNF438, ZNF503, ZNF503-AS2, ZNF511, ZNF574, ZNF622, ZNF726, ZNF99, ZWINT, ADM, ALDOC, BNIP3, CA3, CD209, CSMD3, DDIT4, FCGR2B, FCGR2C, FIGN, GLIS2, SHISA8, SOX5, TBC1D30, TLE6, TLX1, VAT1L, VEGFA, ANXA4, APLN, C1QL4, CCDC102A, CHDH, EGLN3, ENO2, FADS2, HK2, HSPA7, IL17RB, KLF2, LAMC, LINC00263, LOC101928092, LOC102724908, MIR210HG, NRTN, PFKFB4, SCD, SLC4A3, SLC6A8, ZNF215, and ZNF395; optionally wherein the IRAK1 / 4-associated genes are selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, DB1 / 147901903.2 340FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3.

42. The method of claim 41, wherein the subject has elevated expression of one or more IRAK1 / 4-associated genes compared to a healthy control subject and / or a decreased expression of one or more IRAK1 / 4-associated genes compared to a healthy control subject.

43. The method of claim 41 or 42, wherein the subject in need thereof has an elevated expression of one or more IRAK1 / 4-associated genes selected from: PLS3, HSBP1L1, CDC42BPA, PPP2R3A, GNG12, PENK, STC2, DNAJC22, SH3D19, GABRD, RAVER2, ARHGEF26, APBB2, BAI2, DPEP1, LGI2, PIP5K1A, SOX18, BMP4, TMC4, KCNIP3, CCNO, ULK4P2, FAM57A, SCARA3, CERS1, BEND5, HAPLN3, DNMBP, KIAA1522, PIR, GTF3C5 ECHDC3, ICAM1, RAB3A, SDHA, C9orf116, MKI67, LMTK3, MCM10, ADM2, HSD17B14, LOC102724002, KCNH2, PRAME, KIAA1279, LOC101929974, ARHGAP21, SULT2B1, ADCY6, GBF1, TUBGCP2, CD19, SPIRE2, SH3PXD2B, AADAT, FOXC1, ZBED3, TSKU, NRARP, AMIGO2, PCBD1, TCAM1P, FAM57B, LOC101929021, PCK2, CCDC127, MGMT, C6orf147, TGFB1I1, DPP4, ALX4, TACC2, WLS, PACSIN3, NAPA-AS1, LINC00999, BAIAP3, ANKH, VDAC2, TAF3, ECHS1, EFNA3, CORO6, TCTN2, HPS1, DNAJB12, SPIB, SLC29A3, PHGDH, PTMS, TMEM91, SEC24C, HGD, MSS51, TEAD3, LARP4B, ZCCHC24, ARHGEF16, FOXO6, FBXO18, PPRC1, CCDC78, RHBDL1, SPINT1, STON2, NUDT8, NEBL, EPAS1, FAM178A, PI4K2A, SNED1, STAM, PLOD2, TM7SF2, FGD1, PCDHB6, CCNB3, MCMDC2, EDRF1, NRM, PPIF, ATF5, BRD9, B3GALT4, NET1, TMEM169, RPH3AL, DROSHA, RBMS2, POLR3A, TRIP13, LPHN1, ZMIZ1, RP11-344B5.2, HNRNPF, HSD17B7P2, SLIT1, LOC648987, ACTR1A, CCT5, S1PR5, WDFY4, GRK5, SREBF1, STXBP5L, VARS2, GAB2, ZFP36L1, CPNE7, HSPA2, NAT8L, DOK4, IGF1R, KHK, KIRREL2, COMTD1, ZNF488, CASC10, QRICH2, RBM17, LSS, PAX8, PKN3, HELLS, FN3K, CDC42EP1, NFIX, BMS1, STOX1, SEMA4B, SUPV3L1, FAM198A, RCOR2, PDCD4, PPAP2A, DDX12P, ACY3, TSPAN10, NUP155, RIBC2, PLCXD1, TP53INP2, DB1 / 147901903.2 341GOLPH3, WDR70, BTRC, SVIL, DTX4, DUSP5, ECE1, MRPL43, SKP2, SNHG3, MYRF, ZFYVE27, H2AFY2, NOLC1, SLC25A28, WNK2, NDUFS6, SLC30A3, LOC642846, NEURL1B, ARMC4, SFXN3, VASH2, NOTUM, VCL, LOC100506901, CSTF2T, PRICKLE1, ZNF132, GPR153, ZMYND11, DGCR5, OXER1, VTI1A, PCDHGC3, MORC4, EIF3A, PDCD11, SLC38A1, MC1R, CBS, AC002454.1, PDCD6, B4GALNT1, RPP38, SUGT1P1, NEDD4L, PROCA1, SH3PXD2A, JAG2, FGFR3, TMEM191B, SEPHS1, LOC100505761, C21orf58, FADS1, TET1, GBGT1, KAT6B, KIFC2, TAF5, CASP7, PELI3, PP7080, ATN1, KIAA1598, FAM115A, NKX3-2, CHCHD10, GPSM1, LRP4, CDT1, EIF4EBP2, AASS, ABCC6P1, ABCD2, ADAMTS14, AGAP4, AGAP9, AIFM2, AKR1C1, AKR1E2, ANK3, ANKRD33B, ANO6, APBB1IP, ARHGAP19, ARNTL2, ARSG, ARTN, ASCC1, ASUN, BAG3, BEND4, BEX5, BLNK, BTAF1, C10orf10, C10orf12, C10orf76, C10orf91, C15orf38, C2CD4C, C2CD5, C3orf18, CALHM2, CAMK1D, CAPRIN2, CDH2, CDHR1, CEL, CEP72, CES3, CES4A, CHST3, CLIC5, CMAS, CNNM2, CNTN1, COL27A1, COL4A5, CPS1, CRABP1, CTBP2, CUEDC2, CXorf57, DAPK2, DDAH2, DDX11, DDX11-AS1, DENND5B, DHTKD1, DNM1L, DPCD, DPY19L2, DUSP5P1, EBF3, EFEMP2, EGFR, ELK1, EPHB4, FAM155B, FAM175B, FAM21C, FAM45A, FAM53B, FAM84B, FCER2, FGD4, FOXL2, FZD8, GAS1, GPC6, GRIA3, GUCY1B3, GYPE, HDHD3, HES4, HIF1AN, HMGCS1, HMX2, HMX3, HOXB13, HOXB6, HSD17B8, HSH2D, IDE, INPP5A, INPP5F, INPP5J, IPO8, IRAK4, ITPR2, ITPR3, JMJD1C, KAZALD1, KCNQ5, KCNS3, KIAA1324, KIF11, KLHL42, KLLN, KRAS, KREMEN2, LAT, LDB1, LGALS3BP, LINC00477, LIPE, LOC100288152, LOC100506688, LOC100506691, LOC100507487, LOC101927104, LOC101927799, LOC101928913, LOC102723337, LOC102724472, LPCAT1, LRMP, LRRC10B, LRRC20, LRRC27, LTK, LY6G5C, LZTS2, MAP2K6, MASTL, MCIDAS, MCMBP, MDGA2, METTL12, METTL20, MMS19, MPPED2, MRPS16, MRPS35, MSX1, MX1, NDUFB8, NEURL1, NEUROG3, NFKB2, NIM1K, NKD2, NLGN2, NNT, NNT-AS1, NT5DC2, NUDT13, OGDHL, OVOL2, OXCT1, P2RX7, P4HA1, PABPC1L, PANK1, PAOX, PAPD7, PAPSS2, PCDHB13, PCDHB14, PCED1B, PCED1B-AS1, PCSK5, PDLIM1, PEAR1, PFKP, PGAM1, PGAM4, PI15, PITX1, PLEKHA8P1, PLEKHO1, PPFIBP1, PPP2R2D, PPP3CB, PRTFDC1, PSTPIP2, PTENP1, PVRL3, PWWP2B, PXDC1, RNF208, ROBO1, RP11- 184I16.4, RP11-53O19.1, RP11-96H19.1, RPAP3, RTN1, SAMD11, SAMD8, SCAF11, SCD5, SDHAP3, SEC14L2, SEC31B, SEC61A2, SECTM1, SFMBT2, SFXN2, SHANK3, SHISA3, DB1 / 147901903.2 342SHISA7, SIDT1, SKIDA1, SLA2, SLC12A7, SLC16A6, SLC16A9, SLC4A11, SLITRK5, SMAD1, SNHG12, SNORA61, SNORD104, SOX1, SPEF2, SRRM3, SUFU, TARS, TCF7, TEX15, TGFBR3L, THBD, TIAL1, TLX3, TM7SF3, TMEM180, TMEM191C, TMEM255A, TMEM63C, TRIM72, TUBB3, TYSND1, UGT3A2, ULK2, UNC13D, USP54, VENTX, VIM, XPNPEP1, YARS2, YPEL3, ZDHHC16, ZDHHC6, ZNF43, ZNF438, ZNF503, ZNF503-AS2, ZNF511, ZNF574, ZNF622, ZNF726, ZNF99, ZWINT, ADM, ALDOC, BNIP3, CA3, CD209, CSMD3, DDIT4, FCGR2B, FCGR2C, FIGN, GLIS2, SHISA8, SOX5, TBC1D30, TLE6, TLX1, VAT1L, VEGFA, ANXA4, APLN, C1QL4, CCDC102A, CHDH, EGLN3, ENO2, FADS2, HK2, HSPA7, IL17RB, KLF2, LAMC, LINC00263, LOC101928092, LOC102724908, MIR210HG, NRTN, PFKFB4, SCD, SLC4A3, SLC6A8, ZNF215, and ZNF395; optionally wherein the subject in need thereof has elevated expression of one or more IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3.

44. The method of claim 41 or 42, wherein the subject in need thereof has a decreased expression of one or more IRAK1 / 4-associated genes selected from: PLS3, HSBP1L1, CDC42BPA, PPP2R3A, GNG12, PENK, STC2, DNAJC22, SH3D19, GABRD, RAVER2, ARHGEF26, APBB2, BAI2, DPEP1, LGI2, PIP5K1A, SOX18, BMP4, TMC4, KCNIP3, CCNO, ULK4P2, FAM57A, SCARA3, CERS1, BEND5, HAPLN3, DNMBP, KIAA1522, PIR, GTF3C5 ECHDC3, ICAM1, RAB3A, SDHA, C9orf116, MKI67, LMTK3, MCM10, ADM2, HSD17B14, LOC102724002, KCNH2, PRAME, KIAA1279, LOC101929974, ARHGAP21, SULT2B1, ADCY6, GBF1, TUBGCP2, CD19, SPIRE2, SH3PXD2B, AADAT, FOXC1, ZBED3, TSKU, NRARP, AMIGO2, PCBD1, TCAM1P, FAM57B, LOC101929021, PCK2, CCDC127, MGMT, C6orf147, TGFB1I1, DPP4, ALX4, TACC2, WLS, PACSIN3, NAPA-AS1, LINC00999, BAIAP3, ANKH, VDAC2, TAF3, ECHS1, EFNA3, CORO6, TCTN2, HPS1, DNAJB12, SPIB, SLC29A3, PHGDH, PTMS, TMEM91, SEC24C, HGD, MSS51, TEAD3, LARP4B, ZCCHC24, ARHGEF16, FOXO6, FBXO18, PPRC1, CCDC78, RHBDL1, SPINT1, DB1 / 147901903.2 343STON2, NUDT8, NEBL, EPAS1, FAM178A, PI4K2A, SNED1, STAM, PLOD2, TM7SF2, FGD1, PCDHB6, CCNB3, MCMDC2, EDRF1, NRM, PPIF, ATF5, BRD9, B3GALT4, NET1, TMEM169, RPH3AL, DROSHA, RBMS2, POLR3A, TRIP13, LPHN1, ZMIZ1, RP11-344B5.2, HNRNPF, HSD17B7P2, SLIT1, LOC648987, ACTR1A, CCT5, S1PR5, WDFY4, GRK5, SREBF1, STXBP5L, VARS2, GAB2, ZFP36L1, CPNE7, HSPA2, NAT8L, DOK4, IGF1R, KHK, KIRREL2, COMTD1, ZNF488, CASC10, QRICH2, RBM17, LSS, PAX8, PKN3, HELLS, FN3K, CDC42EP1, NFIX, BMS1, STOX1, SEMA4B, SUPV3L1, FAM198A, RCOR2, PDCD4, PPAP2A, DDX12P, ACY3, TSPAN10, NUP155, RIBC2, PLCXD1, TP53INP2, GOLPH3, WDR70, BTRC, SVIL, DTX4, DUSP5, ECE1, MRPL43, SKP2, SNHG3, MYRF, ZFYVE27, H2AFY2, NOLC1, SLC25A28, WNK2, NDUFS6, SLC30A3, LOC642846, NEURL1B, ARMC4, SFXN3, VASH2, NOTUM, VCL, LOC100506901, CSTF2T, PRICKLE1, ZNF132, GPR153, ZMYND11, DGCR5, OXER1, VTI1A, PCDHGC3, MORC4, EIF3A, PDCD11, SLC38A1, MC1R, CBS, AC002454.1, PDCD6, B4GALNT1, RPP38, SUGT1P1, NEDD4L, PROCA1, SH3PXD2A, JAG2, FGFR3, TMEM191B, SEPHS1, LOC100505761, C21orf58, FADS1, TET1, GBGT1, KAT6B, KIFC2, TAF5, CASP7, PELI3, PP7080, ATN1, KIAA1598, FAM115A, NKX3-2, CHCHD10, GPSM1, LRP4, CDT1, EIF4EBP2, AASS, ABCC6P1, ABCD2, ADAMTS14, AGAP4, AGAP9, AIFM2, AKR1C1, AKR1E2, ANK3, ANKRD33B, ANO6, APBB1IP, ARHGAP19, ARNTL2, ARSG, ARTN, ASCC1, ASUN, BAG3, BEND4, BEX5, BLNK, BTAF1, C10orf10, C10orf12, C10orf76, C10orf91, C15orf38, C2CD4C, C2CD5, C3orf18, CALHM2, CAMK1D, CAPRIN2, CDH2, CDHR1, CEL, CEP72, CES3, CES4A, CHST3, CLIC5, CMAS, CNNM2, CNTN1, COL27A1, COL4A5, CPS1, CRABP1, CTBP2, CUEDC2, CXorf57, DAPK2, DDAH2, DDX11, DDX11-AS1, DENND5B, DHTKD1, DNM1L, DPCD, DPY19L2, DUSP5P1, EBF3, EFEMP2, EGFR, ELK1, EPHB4, FAM155B, FAM175B, FAM21C, FAM45A, FAM53B, FAM84B, FCER2, FGD4, FOXL2, FZD8, GAS1, GPC6, GRIA3, GUCY1B3, GYPE, HDHD3, HES4, HIF1AN, HMGCS1, HMX2, HMX3, HOXB13, HOXB6, HSD17B8, HSH2D, IDE, INPP5A, INPP5F, INPP5J, IPO8, IRAK4, ITPR2, ITPR3, JMJD1C, KAZALD1, KCNQ5, KCNS3, KIAA1324, KIF11, KLHL42, KLLN, KRAS, KREMEN2, LAT, LDB1, LGALS3BP, LINC00477, LIPE, LOC100288152, LOC100506688, LOC100506691, LOC100507487, LOC101927104, LOC101927799, LOC101928913, LOC102723337, LOC102724472, LPCAT1, LRMP, LRRC10B, LRRC20, LRRC27, LTK, LY6G5C, LZTS2, MAP2K6, MASTL, MCIDAS, MCMBP, MDGA2, DB1 / 147901903.2 344METTL12, METTL20, MMS19, MPPED2, MRPS16, MRPS35, MSX1, MX1, NDUFB8, NEURL1, NEUROG3, NFKB2, NIM1K, NKD2, NLGN2, NNT, NNT-AS1, NT5DC2, NUDT13, OGDHL, OVOL2, OXCT1, P2RX7, P4HA1, PABPC1L, PANK1, PAOX, PAPD7, PAPSS2, PCDHB13, PCDHB14, PCED1B, PCED1B-AS1, PCSK5, PDLIM1, PEAR1, PFKP, PGAM1, PGAM4, PI15, PITX1, PLEKHA8P1, PLEKHO1, PPFIBP1, PPP2R2D, PPP3CB, PRTFDC1, PSTPIP2, PTENP1, PVRL3, PWWP2B, PXDC1, RNF208, ROBO1, RP11- 184I16.4, RP11-53O19.1, RP11-96H19.1, RPAP3, RTN1, SAMD11, SAMD8, SCAF11, SCD5, SDHAP3, SEC14L2, SEC31B, SEC61A2, SECTM1, SFMBT2, SFXN2, SHANK3, SHISA3, SHISA7, SIDT1, SKIDA1, SLA2, SLC12A7, SLC16A6, SLC16A9, SLC4A11, SLITRK5, SMAD1, SNHG12, SNORA61, SNORD104, SOX1, SPEF2, SRRM3, SUFU, TARS, TCF7, TEX15, TGFBR3L, THBD, TIAL1, TLX3, TM7SF3, TMEM180, TMEM191C, TMEM255A, TMEM63C, TRIM72, TUBB3, TYSND1, UGT3A2, ULK2, UNC13D, USP54, VENTX, VIM, XPNPEP1, YARS2, YPEL3, ZDHHC16, ZDHHC6, ZNF43, ZNF438, ZNF503, ZNF503-AS2, ZNF511, ZNF574, ZNF622, ZNF726, ZNF99, ZWINT, ADM, ALDOC, BNIP3, CA3, CD209, CSMD3, DDIT4, FCGR2B, FCGR2C, FIGN, GLIS2, SHISA8, SOX5, TBC1D30, TLE6, TLX1, VAT1L, VEGFA, ANXA4, APLN, C1QL4, CCDC102A, CHDH, EGLN3, ENO2, FADS2, HK2, HSPA7, IL17RB, KLF2, LAMC, LINC00263, LOC101928092, LOC102724908, MIR210HG, NRTN, PFKFB4, SCD, SLC4A3, SLC6A8, ZNF215, and ZNF395, optionally wherein the subject in need thereof has decreased expression of one or more IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3.

45. The method of any one of claims 41 to 44, wherein Compound 8 decreases the expression of one or more IRAK1 / 4-associated genes in the subject, and / or increases the expression of one or more IRAK1 / 4-associated genes in the subject. DB1 / 147901903.2 34546. The method of any one of claims 41 to 44, wherein Compound 8 decreases the expression of one or more IRAK1 / 4-associated genes found to be elevated in the subject, and / or increases the expression of one or more IRAK1 / 4-associated genes found to be decreased in the subject.

47. The method of claim 45 or 46, wherein the administration of Compound 8 decreases the expression of the one or more IRAK1 / 4-associated genes found to be elevated in the subject before the administration of Compound 8, and / or increases the expression of the one or more IRAK1 / 4-associated genes found to be decreased in the subject before the administration of Compound 8.

48. The method of any one of claims 45 to 47, wherein Compound 8 decreases the expression of one or more IRAK1 / 4-associated genes found to be elevated in the subject compared to a healthy control subject, and / or increases the expression of one or more IRAK1 / 4- associated genes found to be decreased in the subject compared to a healthy control subject.

49. The method of any one of claims 45 to 48, wherein Compound 8 decreases the expression of one or more IRAK1 / 4-associated genes selected from: PLS3, HSBP1L1, CDC42BPA, PPP2R3A, GNG12, PENK, STC2, DNAJC22, SH3D19, GABRD, RAVER2, ARHGEF26, APBB2, BAI2, DPEP1, LGI2, PIP5K1A, SOX18, BMP4, TMC4, KCNIP3, CCNO, ULK4P2, FAM57A, SCARA3, CERS1, BEND5, HAPLN3, DNMBP, KIAA1522, PIR, GTF3C5 ECHDC3, ICAM1, RAB3A, SDHA, C9orf116, MKI67, LMTK3, MCM10, ADM2, HSD17B14, LOC102724002, KCNH2, PRAME, KIAA1279, LOC101929974, ARHGAP21, SULT2B1, ADCY6, GBF1, TUBGCP2, CD19, SPIRE2, SH3PXD2B, AADAT, FOXC1, ZBED3, TSKU, NRARP, AMIGO2, PCBD1, TCAM1P, FAM57B, LOC101929021, PCK2, CCDC127, MGMT, C6orf147, TGFB1I1, DPP4, ALX4, TACC2, WLS, PACSIN3, NAPA-AS1, LINC00999, BAIAP3, ANKH, VDAC2, TAF3, ECHS1, EFNA3, CORO6, TCTN2, HPS1, DNAJB12, SPIB, SLC29A3, PHGDH, PTMS, TMEM91, SEC24C, HGD, MSS51, TEAD3, LARP4B, ZCCHC24, ARHGEF16, FOXO6, FBXO18, PPRC1, CCDC78, RHBDL1, SPINT1, STON2, NUDT8, NEBL, EPAS1, FAM178A, PI4K2A, SNED1, STAM, PLOD2, TM7SF2, FGD1, PCDHB6, CCNB3, MCMDC2, EDRF1, NRM, PPIF, ATF5, BRD9, B3GALT4, NET1, DB1 / 147901903.2 346TMEM169, RPH3AL, DROSHA, RBMS2, POLR3A, TRIP13, LPHN1, ZMIZ1, RP11-344B5.2, HNRNPF, HSD17B7P2, SLIT1, LOC648987, ACTR1A, CCT5, S1PR5, WDFY4, GRK5, SREBF1, STXBP5L, VARS2, GAB2, ZFP36L1, CPNE7, HSPA2, NAT8L, DOK4, IGF1R, KHK, KIRREL2, COMTD1, ZNF488, CASC10, QRICH2, RBM17, LSS, PAX8, PKN3, HELLS, FN3K, CDC42EP1, NFIX, BMS1, STOX1, SEMA4B, SUPV3L1, FAM198A, RCOR2, PDCD4, PPAP2A, DDX12P, ACY3, TSPAN10, NUP155, RIBC2, PLCXD1, TP53INP2, GOLPH3, WDR70, BTRC, SVIL, DTX4, DUSP5, ECE1, MRPL43, SKP2, SNHG3, MYRF, ZFYVE27, H2AFY2, NOLC1, SLC25A28, WNK2, NDUFS6, SLC30A3, LOC642846, NEURL1B, ARMC4, SFXN3, VASH2, NOTUM, VCL, LOC100506901, CSTF2T, PRICKLE1, ZNF132, GPR153, ZMYND11, DGCR5, OXER1, VTI1A, PCDHGC3, MORC4, EIF3A, PDCD11, SLC38A1, MC1R, CBS, AC002454.1, PDCD6, B4GALNT1, RPP38, SUGT1P1, NEDD4L, PROCA1, SH3PXD2A, JAG2, FGFR3, TMEM191B, SEPHS1, LOC100505761, C21orf58, FADS1, TET1, GBGT1, KAT6B, KIFC2, TAF5, CASP7, PELI3, PP7080, ATN1, KIAA1598, FAM115A, NKX3-2, CHCHD10, GPSM1, LRP4, CDT1, EIF4EBP2, AASS, ABCC6P1, ABCD2, ADAMTS14, AGAP4, AGAP9, AIFM2, AKR1C1, AKR1E2, ANK3, ANKRD33B, ANO6, APBB1IP, ARHGAP19, ARNTL2, ARSG, ARTN, ASCC1, ASUN, BAG3, BEND4, BEX5, BLNK, BTAF1, C10orf10, C10orf12, C10orf76, C10orf91, C15orf38, C2CD4C, C2CD5, C3orf18, CALHM2, CAMK1D, CAPRIN2, CDH2, CDHR1, CEL, CEP72, CES3, CES4A, CHST3, CLIC5, CMAS, CNNM2, CNTN1, COL27A1, COL4A5, CPS1, CRABP1, CTBP2, CUEDC2, CXorf57, DAPK2, DDAH2, DDX11, DDX11-AS1, DENND5B, DHTKD1, DNM1L, DPCD, DPY19L2, DUSP5P1, EBF3, EFEMP2, EGFR, ELK1, EPHB4, FAM155B, FAM175B, FAM21C, FAM45A, FAM53B, FAM84B, FCER2, FGD4, FOXL2, FZD8, GAS1, GPC6, GRIA3, GUCY1B3, GYPE, HDHD3, HES4, HIF1AN, HMGCS1, HMX2, HMX3, HOXB13, HOXB6, HSD17B8, HSH2D, IDE, INPP5A, INPP5F, INPP5J, IPO8, IRAK4, ITPR2, ITPR3, JMJD1C, KAZALD1, KCNQ5, KCNS3, KIAA1324, KIF11, KLHL42, KLLN, KRAS, KREMEN2, LAT, LDB1, LGALS3BP, LINC00477, LIPE, LOC100288152, LOC100506688, LOC100506691, LOC100507487, LOC101927104, LOC101927799, LOC101928913, LOC102723337, LOC102724472, LPCAT1, LRMP, LRRC10B, LRRC20, LRRC27, LTK, LY6G5C, LZTS2, MAP2K6, MASTL, MCIDAS, MCMBP, MDGA2, METTL12, METTL20, MMS19, MPPED2, MRPS16, MRPS35, MSX1, MX1, NDUFB8, NEURL1, NEUROG3, NFKB2, NIM1K, NKD2, NLGN2, NNT, NNT-AS1, NT5DC2, DB1 / 147901903.2 347NUDT13, OGDHL, OVOL2, OXCT1, P2RX7, P4HA1, PABPC1L, PANK1, PAOX, PAPD7, PAPSS2, PCDHB13, PCDHB14, PCED1B, PCED1B-AS1, PCSK5, PDLIM1, PEAR1, PFKP, PGAM1, PGAM4, PI15, PITX1, PLEKHA8P1, PLEKHO1, PPFIBP1, PPP2R2D, PPP3CB, PRTFDC1, PSTPIP2, PTENP1, PVRL3, PWWP2B, PXDC1, RNF208, ROBO1, RP11- 184I16.4, RP11-53O19.1, RP11-96H19.1, RPAP3, RTN1, SAMD11, SAMD8, SCAF11, SCD5, SDHAP3, SEC14L2, SEC31B, SEC61A2, SECTM1, SFMBT2, SFXN2, SHANK3, SHISA3, SHISA7, SIDT1, SKIDA1, SLA2, SLC12A7, SLC16A6, SLC16A9, SLC4A11, SLITRK5, SMAD1, SNHG12, SNORA61, SNORD104, SOX1, SPEF2, SRRM3, SUFU, TARS, TCF7, TEX15, TGFBR3L, THBD, TIAL1, TLX3, TM7SF3, TMEM180, TMEM191C, TMEM255A, TMEM63C, TRIM72, TUBB3, TYSND1, UGT3A2, ULK2, UNC13D, USP54, VENTX, VIM, XPNPEP1, YARS2, YPEL3, ZDHHC16, ZDHHC6, ZNF43, ZNF438, ZNF503, ZNF503-AS2, ZNF511, ZNF574, ZNF622, ZNF726, ZNF99, ZWINT, ADM, ALDOC, BNIP3, CA3, CD209, CSMD3, DDIT4, FCGR2B, FCGR2C, FIGN, GLIS2, SHISA8, SOX5, TBC1D30, TLE6, TLX1, VAT1L, VEGFA, ANXA4, APLN, C1QL4, CCDC102A, CHDH, EGLN3, ENO2, FADS2, HK2, HSPA7, IL17RB, KLF2, LAMC, LINC00263, LOC101928092, LOC102724908, MIR210HG, NRTN, PFKFB4, SCD, SLC4A3, SLC6A8, ZNF215, and ZNF395 in the subject; optionally wherein the compound decreases the expression of one or more IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3 in the subject.

50. The method of any one of claims 45 to 48, wherein Compound 8 increases the expression of one or more IRAK1 / 4-associated genes selected from: PLS3, HSBP1L1, CDC42BPA, PPP2R3A, GNG12, PENK, STC2, DNAJC22, SH3D19, GABRD, RAVER2, ARHGEF26, APBB2, BAI2, DPEP1, LGI2, PIP5K1A, SOX18, BMP4, TMC4, KCNIP3, CCNO, ULK4P2, FAM57A, SCARA3, CERS1, BEND5, HAPLN3, DNMBP, KIAA1522, PIR, GTF3C5 ECHDC3, ICAM1, RAB3A, SDHA, C9orf116, MKI67, LMTK3, MCM10, ADM2, HSD17B14, LOC102724002, KCNH2, PRAME, KIAA1279, LOC101929974, ARHGAP21, DB1 / 147901903.2 348SULT2B1, ADCY6, GBF1, TUBGCP2, CD19, SPIRE2, SH3PXD2B, AADAT, FOXC1, ZBED3, TSKU, NRARP, AMIGO2, PCBD1, TCAM1P, FAM57B, LOC101929021, PCK2, CCDC127, MGMT, C6orf147, TGFB1I1, DPP4, ALX4, TACC2, WLS, PACSIN3, NAPA-AS1, LINC00999, BAIAP3, ANKH, VDAC2, TAF3, ECHS1, EFNA3, CORO6, TCTN2, HPS1, DNAJB12, SPIB, SLC29A3, PHGDH, PTMS, TMEM91, SEC24C, HGD, MSS51, TEAD3, LARP4B, ZCCHC24, ARHGEF16, FOXO6, FBXO18, PPRC1, CCDC78, RHBDL1, SPINT1, STON2, NUDT8, NEBL, EPAS1, FAM178A, PI4K2A, SNED1, STAM, PLOD2, TM7SF2, FGD1, PCDHB6, CCNB3, MCMDC2, EDRF1, NRM, PPIF, ATF5, BRD9, B3GALT4, NET1, TMEM169, RPH3AL, DROSHA, RBMS2, POLR3A, TRIP13, LPHN1, ZMIZ1, RP11-344B5.2, HNRNPF, HSD17B7P2, SLIT1, LOC648987, ACTR1A, CCT5, S1PR5, WDFY4, GRK5, SREBF1, STXBP5L, VARS2, GAB2, ZFP36L1, CPNE7, HSPA2, NAT8L, DOK4, IGF1R, KHK, KIRREL2, COMTD1, ZNF488, CASC10, QRICH2, RBM17, LSS, PAX8, PKN3, HELLS, FN3K, CDC42EP1, NFIX, BMS1, STOX1, SEMA4B, SUPV3L1, FAM198A, RCOR2, PDCD4, PPAP2A, DDX12P, ACY3, TSPAN10, NUP155, RIBC2, PLCXD1, TP53INP2, GOLPH3, WDR70, BTRC, SVIL, DTX4, DUSP5, ECE1, MRPL43, SKP2, SNHG3, MYRF, ZFYVE27, H2AFY2, NOLC1, SLC25A28, WNK2, NDUFS6, SLC30A3, LOC642846, NEURL1B, ARMC4, SFXN3, VASH2, NOTUM, VCL, LOC100506901, CSTF2T, PRICKLE1, ZNF132, GPR153, ZMYND11, DGCR5, OXER1, VTI1A, PCDHGC3, MORC4, EIF3A, PDCD11, SLC38A1, MC1R, CBS, AC002454.1, PDCD6, B4GALNT1, RPP38, SUGT1P1, NEDD4L, PROCA1, SH3PXD2A, JAG2, FGFR3, TMEM191B, SEPHS1, LOC100505761, C21orf58, FADS1, TET1, GBGT1, KAT6B, KIFC2, TAF5, CASP7, PELI3, PP7080, ATN1, KIAA1598, FAM115A, NKX3-2, CHCHD10, GPSM1, LRP4, CDT1, EIF4EBP2, AASS, ABCC6P1, ABCD2, ADAMTS14, AGAP4, AGAP9, AIFM2, AKR1C1, AKR1E2, ANK3, ANKRD33B, ANO6, APBB1IP, ARHGAP19, ARNTL2, ARSG, ARTN, ASCC1, ASUN, BAG3, BEND4, BEX5, BLNK, BTAF1, C10orf10, C10orf12, C10orf76, C10orf91, C15orf38, C2CD4C, C2CD5, C3orf18, CALHM2, CAMK1D, CAPRIN2, CDH2, CDHR1, CEL, CEP72, CES3, CES4A, CHST3, CLIC5, CMAS, CNNM2, CNTN1, COL27A1, COL4A5, CPS1, CRABP1, CTBP2, CUEDC2, CXorf57, DAPK2, DDAH2, DDX11, DDX11-AS1, DENND5B, DHTKD1, DNM1L, DPCD, DPY19L2, DUSP5P1, EBF3, EFEMP2, EGFR, ELK1, EPHB4, FAM155B, FAM175B, FAM21C, FAM45A, FAM53B, FAM84B, FCER2, FGD4, FOXL2, FZD8, GAS1, GPC6, GRIA3, GUCY1B3, GYPE, HDHD3, HES4, HIF1AN, HMGCS1, HMX2, DB1 / 147901903.2 349HMX3, HOXB13, HOXB6, HSD17B8, HSH2D, IDE, INPP5A, INPP5F, INPP5J, IPO8, IRAK4, ITPR2, ITPR3, JMJD1C, KAZALD1, KCNQ5, KCNS3, KIAA1324, KIF11, KLHL42, KLLN, KRAS, KREMEN2, LAT, LDB1, LGALS3BP, LINC00477, LIPE, LOC100288152, LOC100506688, LOC100506691, LOC100507487, LOC101927104, LOC101927799, LOC101928913, LOC102723337, LOC102724472, LPCAT1, LRMP, LRRC10B, LRRC20, LRRC27, LTK, LY6G5C, LZTS2, MAP2K6, MASTL, MCIDAS, MCMBP, MDGA2, METTL12, METTL20, MMS19, MPPED2, MRPS16, MRPS35, MSX1, MX1, NDUFB8, NEURL1, NEUROG3, NFKB2, NIM1K, NKD2, NLGN2, NNT, NNT-AS1, NT5DC2, NUDT13, OGDHL, OVOL2, OXCT1, P2RX7, P4HA1, PABPC1L, PANK1, PAOX, PAPD7, PAPSS2, PCDHB13, PCDHB14, PCED1B, PCED1B-AS1, PCSK5, PDLIM1, PEAR1, PFKP, PGAM1, PGAM4, PI15, PITX1, PLEKHA8P1, PLEKHO1, PPFIBP1, PPP2R2D, PPP3CB, PRTFDC1, PSTPIP2, PTENP1, PVRL3, PWWP2B, PXDC1, RNF208, ROBO1, RP11- 184I16.4, RP11-53O19.1, RP11-96H19.1, RPAP3, RTN1, SAMD11, SAMD8, SCAF11, SCD5, SDHAP3, SEC14L2, SEC31B, SEC61A2, SECTM1, SFMBT2, SFXN2, SHANK3, SHISA3, SHISA7, SIDT1, SKIDA1, SLA2, SLC12A7, SLC16A6, SLC16A9, SLC4A11, SLITRK5, SMAD1, SNHG12, SNORA61, SNORD104, SOX1, SPEF2, SRRM3, SUFU, TARS, TCF7, TEX15, TGFBR3L, THBD, TIAL1, TLX3, TM7SF3, TMEM180, TMEM191C, TMEM255A, TMEM63C, TRIM72, TUBB3, TYSND1, UGT3A2, ULK2, UNC13D, USP54, VENTX, VIM, XPNPEP1, YARS2, YPEL3, ZDHHC16, ZDHHC6, ZNF43, ZNF438, ZNF503, ZNF503-AS2, ZNF511, ZNF574, ZNF622, ZNF726, ZNF99, ZWINT, ADM, ALDOC, BNIP3, CA3, CD209, CSMD3, DDIT4, FCGR2B, FCGR2C, FIGN, GLIS2, SHISA8, SOX5, TBC1D30, TLE6, TLX1, VAT1L, VEGFA, ANXA4, APLN, C1QL4, CCDC102A, CHDH, EGLN3, ENO2, FADS2, HK2, HSPA7, IL17RB, KLF2, LAMC, LINC00263, LOC101928092, LOC102724908, MIR210HG, NRTN, PFKFB4, SCD, SLC4A3, SLC6A8, ZNF215, and ZNF395 in the subject; optionally wherein the compound increases the expression of one or more IRAK1 / 4-associated genes selected from: KRAS, SOX5, HMX2, TACC2, AIFM2, ZNF438, FGD4, GRK5, ANK3, ZNF622, PWWP2B, SFXN3, SLC29A3, COL27A1, ARHGAP21, PDLIM1, CAMK1D, SCAF11, DNAJB12, TUBGCP2, DNMBP, JMJD1C, ELK1, SFMBT2, NRARP, DDIT4, DUSP5, INPP5A, BRD9, ZFYVE27, LRMP, SLC38A1, SLC12A7, ZMIZ1, ANO6, PRICKLE1, CALHM2, LINC00477, NIM1K, COMTD, ECHDC3, PAOX, LPCAT1, ARSG, PSTPIP2, VENTX, AMIGO2, PCED1B, PCED1B−AS1, and BAG3 in the subject. DB1 / 147901903.2 35051. A method of determining whether a subject with a disease or disorder selected from an inflammatory disease or disorder, and a cancer selected from acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), can be treated by the administration of Compound 8 or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, the method comprising: determining whether the subject has an elevated expression of one or more NFκB- associated genes, and / or a decreased expression of one or more NFκB-associated genes, wherein the NFκB-associated genes are selected from: A4, ABCA1, ABCB1, ABCB4, ABCB9, ABCC6, ABCG5, ABCG8, ADAM19, ADH1A, ADORA1, ADORA2A, ADRA2B. AFP, AGER, AGT, AHCTF1, AICDA, AKR1C1, ALOX12, ALOX5, AMACR, AMH, ANGPT1, APOBEC2, APOC3, APOD, APOE, AQP4, AR, ARFRP1, ART1, ASPH, ASS1, ATP1A2, B2M, BACE1, BAX, BCL2, BCL2A1, BCL2L1, BCL2L11, BCL3, BDKRB1, BDKRB1, BDNF, BGN, BLIMP1 / PRDM1, BLNK, BLR1, BMI1, BMP2, BMP4, BNIP3, BRCA2, BTK, C3, C4A, C4BPA, C69, CALCB, CASP4, CAV1, CCL1, CCL15, CCL17, CCL19, CCL2, CCL20, CCL22, CCL23, CCL28, CCL3, CCL4, CCL5, CCND1, CCND2, CCND3, CCR5, CCR7, CD209, CD274, CD38, CD3G, CD40, CD40LG, CD44, CD48, CD54, CD80, CD83, CD86, CDK6, CDKN1A, CDX1, CEBPD, CFB, CFLAR, CGM3, CHI3L1, CIDEA, CLDN2, COL1A2, CR2, CREB3, CRP, CSF1, CSF2, CSF3, CTSB, CTSL1, CXCL1, CXCL10, CXCL11, CXCL3, CXCL5, CXCL6, CXCL9, CYP19A1, CYP27B1, CYP2C11, CYP2E1, CYP7B1, DCTN4, DEFB2, DIO2, DMP1, DNASE1L2, DPYD, DUSP1, E2F3, EBI3, EDN1, EGFR, EGR1, ELF3, ENG, ENO2, EPHA1, EPO, ERBB2, ERVWE1, F11R, F3, F8, FABP6, FAM148A, FAS, FASLG, FCER2. FCER2 / CD23, FCGRT, FGF8, FN1, FOS, FSTL3, FTH1, G6PC, G6PD, GAD1, GADD45B, GATA3, GBP1, GCLC, GCLM, GCNT1, GJB1, GNAI2, GNB2L1, GNRH2, GRIN1, GRIN2A, GRM2, GRO-beta, GRO-gamma, GSTP1, GUCY1A2, GZMB, HAMP, HAS1, HBE1, HBZ, HGF, HIF1A, HLA-B, HLA-G, HMGN1, HMOX1, HOXA9, HPSE, HSD11B2, HSD17B8, HSP90AA1, ICOS, IDO1, IER2, IER3, IFI44L, IFNB, IFNG, IGFBP1, IGFBP2, IGHE, IGHG1, IGHG2, IGHG4, IGKC, Iigp1, IL10, IL11, IL12A, IL12B, IL13, IL15, IL17, IL1A, IL1B, IL1RN, IL2, IL23A, IL27, IL2RA, IL6, IL8, IL8RA, IL8RB, IL9, INHBA, IRF1, IRF2, IRF4, IRF7, JMJD3, JUNB, KC, KCNK5, KCNN2, KISS1, KITLG, KLF10, KLK3, KLRA1, KRT15, KRT3, KRT5, KRT6B, LAMB2, DB1 / 147901903.2 351LBP, LCN2, LEF1, LGALS3, LIPG, LTA, LTB, LTF, LYZ, MADCAM1, MAP4K1, MBP, MDK, MMP1, MMP3, MMP9, MT3, MTHFR, MUC2, MX1, MYB, MYC, MYLK, MYOZ1, NCAM, NFKB1, NFKB2, NFKBIA, NFKBIE, NFKBIZ, NGFB, NK4, NLRP2, NOD2, NOS1, NOS2A, NOX1, NPY1R, NQO1, NR3C1, NR4A2, NRG1, NUAK2, OLR1, OPN1SW, OPRD1, OPRM1, ORM1, Osterix, OXTR, PAFAH2, PAX8, PDE7A, PDGFB, PDYN, PENK, PGK1, PGLYRP1, PGR, PI3KAP1, PIGF, pIgR, PIK3CA, PIM1, PLA2, PLAU, PLCD1, PLK3, POMC, PPARGC1B, PPP5C, PRF1, PRKACA, PRKCD, PRL, PSMB9, PSME1, PSME2, PTAFR,, PTEN, PTGDS, PTGES, PTGIS, PTGS2, PTHLH, PTPN1, PTPN13, PTS, PTX3, PYCARD, RAG1, RAG2, RBBP4, Rdh1, Rdh7, REL, RELB, REV3L, RIPK2, S100A10, S100A4, S100A6, SAA1, SAA2, SAA, SAT1, SCNN1A, SDC4, SELE, SELP, SELS, SENP2, SERPINA1, SERPINA2, SERPINA3, SERPINB1, SERPINE1, PAI-1, SERPINE2, SH3BGRL, SKALP, PI3, SKP2, SLC11A2, SLC16A1, SLC3A2, SLC6A6, Slfn2, SNAI1, SOD1, SOD2, SOX9, SPATA19, SPI1, SPP1, ST6GAL1, ST8SIA1, STAT5A, SUPV3L1, TACR1, TAP1, TAPBP, TCRB, TERT, TF, TFEC, TFF3, TFPI2, TGM1, TGM2, THBS1, THBS2, TICAM1, TIFA, TLR2, TLR9, TNC, TN, TNFAIP2, TNFAIP3, TNFRSF1B, TNFRSF4, TNFRSF9, TNFSF10, TNFSF13B, TNFSF13B, TNFSF15, TNIP1, TNIP3, TP53, TRAF1, TRAF2, TREM1, TRPC1, TWIST1, UBE2M, UCP2, UGCGL1, UPK1B, UPP1, VCAM1, VEGFC, VIM, VPS53, WNT10B, WT1, XDH, XIAP, YY1, and ZNF366.

52. The method of claim 51, wherein the subject has elevated expression of one or more NFκB-associated genes compared to a healthy control subject and / or a decreased expression of one or more IRAK1 / 4-associated genes compared to a healthy control subject.

53. The method of claim 51 or 52, wherein the subject in need thereof has an elevated expression of one or more NFκB-associated genes selected from: A4, ABCA1, ABCB1, ABCB4, ABCB9, ABCC6, ABCG5, ABCG8, ADAM19, ADH1A, ADORA1, ADORA2A, ADRA2B. AFP, AGER, AGT, AHCTF1, AICDA, AKR1C1, ALOX12, ALOX5, AMACR, AMH, ANGPT1, APOBEC2, APOC3, APOD, APOE, AQP4, AR, ARFRP1, ART1, ASPH, ASS1, ATP1A2, B2M, BACE1, BAX, BCL2, BCL2A1, BCL2L1, BCL2L11, BCL3, BDKRB1, BDKRB1, BDNF, BGN, BLIMP1 / PRDM1, BLNK, BLR1, BMI1, BMP2, BMP4, BNIP3, BRCA2, BTK, C3, C4A, C4BPA, C69, CALCB, CASP4, CAV1, CCL1, CCL15, CCL17, DB1 / 147901903.2 352CCL19, CCL2, CCL20, CCL22, CCL23, CCL28, CCL3, CCL4, CCL5, CCND1, CCND2, CCND3, CCR5, CCR7, CD209, CD274, CD38, CD3G, CD40, CD40LG, CD44, CD48, CD54, CD80, CD83, CD86, CDK6, CDKN1A, CDX1, CEBPD, CFB, CFLAR, CGM3, CHI3L1, CIDEA, CLDN2, COL1A2, CR2, CREB3, CRP, CSF1, CSF2, CSF3, CTSB, CTSL1, CXCL1, CXCL10, CXCL11, CXCL3, CXCL5, CXCL6, CXCL9, CYP19A1, CYP27B1, CYP2C11, CYP2E1, CYP7B1, DCTN4, DEFB2, DIO2, DMP1, DNASE1L2, DPYD, DUSP1, E2F3, EBI3, EDN1, EGFR, EGR1, ELF3, ENG, ENO2, EPHA1, EPO, ERBB2, ERVWE1, F11R, F3, F8, FABP6, FAM148A, FAS, FASLG, FCER2. FCER2 / CD23, FCGRT, FGF8, FN1, FOS, FSTL3, FTH1, G6PC, G6PD, GAD1, GADD45B, GATA3, GBP1, GCLC, GCLM, GCNT1, GJB1, GNAI2, GNB2L1, GNRH2, GRIN1, GRIN2A, GRM2, GRO-beta, GRO-gamma, GSTP1, GUCY1A2, GZMB, HAMP, HAS1, HBE1, HBZ, HGF, HIF1A, HLA-B, HLA-G, HMGN1, HMOX1, HOXA9, HPSE, HSD11B2, HSD17B8, HSP90AA1, ICOS, IDO1, IER2, IER3, IFI44L, IFNB, IFNG, IGFBP1, IGFBP2, IGHE, IGHG1, IGHG2, IGHG4, IGKC, Iigp1, IL10, IL11, IL12A, IL12B, IL13, IL15, IL17, IL1A, IL1B, IL1RN, IL2, IL23A, IL27, IL2RA, IL6, IL8, IL8RA, IL8RB, IL9, INHBA, IRF1, IRF2, IRF4, IRF7, JMJD3, JUNB, KC, KCNK5, KCNN2, KISS1, KITLG, KLF10, KLK3, KLRA1, KRT15, KRT3, KRT5, KRT6B, LAMB2, LBP, LCN2, LEF1, LGALS3, LIPG, LTA, LTB, LTF, LYZ, MADCAM1, MAP4K1, MBP, MDK, MMP1, MMP3, MMP9, MT3, MTHFR, MUC2, MX1, MYB, MYC, MYLK, MYOZ1, NCAM, NFKB1, NFKB2, NFKBIA, NFKBIE, NFKBIZ, NGFB, NK4, NLRP2, NOD2, NOS1, NOS2A, NOX1, NPY1R, NQO1, NR3C1, NR4A2, NRG1, NUAK2, OLR1, OPN1SW, OPRD1, OPRM1, ORM1, Osterix, OXTR, PAFAH2, PAX8, PDE7A, PDGFB, PDYN, PENK, PGK1, PGLYRP1, PGR, PI3KAP1, PIGF, pIgR, PIK3CA, PIM1, PLA2, PLAU, PLCD1, PLK3, POMC, PPARGC1B, PPP5C, PRF1, PRKACA, PRKCD, PRL, PSMB9, PSME1, PSME2, PTAFR, PTEN, PTGDS, PTGES, PTGIS, PTGS2, PTHLH, PTPN1, PTPN13, PTS, PTX3, PYCARD, RAG1, RAG2, RBBP4, Rdh1, Rdh7, REL, RELB, REV3L, RIPK2, S100A10, S100A4, S100A6, SAA1, SAA2, SAA, SAT1, SCNN1A, SDC4, SELE, SELP, SELS, SENP2, SERPINA1, SERPINA2, SERPINA3, SERPINB1, SERPINE1, PAI-1, SERPINE2, SH3BGRL, SKALP, PI3, SKP2, SLC11A2, SLC16A1, SLC3A2, SLC6A6, Slfn2, SNAI1, SOD1, SOD2, SOX9, SPATA19, SPI1, SPP1, ST6GAL1, ST8SIA1, STAT5A, SUPV3L1, TACR1, TAP1, TAPBP, TCRB, TERT, TF, TFEC, TFF3, TFPI2, TGM1, TGM2, THBS1, THBS2, TICAM1, TIFA, TLR2, TLR9, TNC, TN, TNFAIP2, TNFAIP3, TNFRSF1B, TNFRSF4, TNFRSF9, DB1 / 147901903.2 353TNFSF10, TNFSF13B, TNFSF13B, TNFSF15, TNIP1, TNIP3, TP53, TRAF1, TRAF2, TREM1, TRPC1, TWIST1, UBE2M, UCP2, UGCGL1, UPK1B, UPP1, VCAM1, VEGFC, VIM, VPS53, WNT10B, WT1, XDH, XIAP, YY1, and ZNF366.

54. The method of claim 51 or 52, wherein the subject in need thereof has a decreased expression of one or more NFκB-associated genes selected from: A4, ABCA1, ABCB1, ABCB4, ABCB9, ABCC6, ABCG5, ABCG8, ADAM19, ADH1A, ADORA1, ADORA2A, ADRA2B. AFP, AGER, AGT, AHCTF1, AICDA, AKR1C1, ALOX12, ALOX5, AMACR, AMH, ANGPT1, APOBEC2, APOC3, APOD, APOE, AQP4, AR, ARFRP1, ART1, ASPH, ASS1, ATP1A2, B2M, BACE1, BAX, BCL2, BCL2A1, BCL2L1, BCL2L11, BCL3, BDKRB1, BDKRB1, BDNF, BGN, BLIMP1 / PRDM1, BLNK, BLR1, BMI1, BMP2, BMP4, BNIP3, BRCA2, BTK, C3, C4A, C4BPA, C69, CALCB, CASP4, CAV1, CCL1, CCL15, CCL17, CCL19, CCL2, CCL20, CCL22, CCL23, CCL28, CCL3, CCL4, CCL5, CCND1, CCND2, CCND3, CCR5, CCR7, CD209, CD274, CD38, CD3G, CD40, CD40LG, CD44, CD48, CD54, CD80, CD83, CD86, CDK6, CDKN1A, CDX1, CEBPD, CFB, CFLAR, CGM3, CHI3L1, CIDEA, CLDN2, COL1A2, CR2, CREB3, CRP, CSF1, CSF2, CSF3, CTSB, CTSL1, CXCL1, CXCL10, CXCL11, CXCL3, CXCL5, CXCL6, CXCL9, CYP19A1, CYP27B1, CYP2C11, CYP2E1, CYP7B1, DCTN4, DEFB2, DIO2, DMP1, DNASE1L2, DPYD, DUSP1, E2F3, EBI3, EDN1, EGFR, EGR1, ELF3, ENG, ENO2, EPHA1, EPO, ERBB2, ERVWE1, F11R, F3, F8, FABP6, FAM148A, FAS, FASLG, FCER2. FCER2 / CD23, FCGRT, FGF8, FN1, FOS, FSTL3, FTH1, G6PC, G6PD, GAD1, GADD45B, GATA3, GBP1, GCLC, GCLM, GCNT1, GJB1, GNAI2, GNB2L1, GNRH2, GRIN1, GRIN2A, GRM2, GRO-beta, GRO-gamma, GSTP1, GUCY1A2, GZMB, HAMP, HAS1, HBE1, HBZ, HGF, HIF1A, HLA-B, HLA-G, HMGN1, HMOX1, HOXA9, HPSE, HSD11B2, HSD17B8, HSP90AA1, ICOS, IDO1, IER2, IER3, IFI44L, IFNB, IFNG, IGFBP1, IGFBP2, IGHE, IGHG1, IGHG2, IGHG4, IGKC, Iigp1, IL10, IL11, IL12A, IL12B, IL13, IL15, IL17, IL1A, IL1B, IL1RN, IL2, IL23A, IL27, IL2RA, IL6, IL8, IL8RA, IL8RB, IL9, INHBA, IRF1, IRF2, IRF4, IRF7, JMJD3, JUNB, KC, KCNK5, KCNN2, KISS1, KITLG, KLF10, KLK3, KLRA1, KRT15, KRT3, KRT5, KRT6B, LAMB2, LBP, LCN2, LEF1, LGALS3, LIPG, LTA, LTB, LTF, LYZ, MADCAM1, MAP4K1, MBP, MDK, MMP1, MMP3, MMP9, MT3, MTHFR, MUC2, MX1, MYB, MYC, MYLK, MYOZ1, NCAM, NFKB1, NFKB2, NFKBIA, NFKBIE, NFKBIZ, NGFB, NK4, NLRP2, NOD2, NOS1, DB1 / 147901903.2 354NOS2A, NOX1, NPY1R, NQO1, NR3C1, NR4A2, NRG1, NUAK2, OLR1, OPN1SW, OPRD1, OPRM1, ORM1, Osterix, OXTR, PAFAH2, PAX8, PDE7A, PDGFB, PDYN, PENK, PGK1, PGLYRP1, PGR, PI3KAP1, PIGF, pIgR, PIK3CA, PIM1, PLA2, PLAU, PLCD1, PLK3, POMC, PPARGC1B, PPP5C, PRF1, PRKACA, PRKCD, PRL, PSMB9, PSME1, PSME2, PTAFR,, PTEN, PTGDS, PTGES, PTGIS, PTGS2, PTHLH, PTPN1, PTPN13, PTS, PTX3, PYCARD, RAG1, RAG2, RBBP4, Rdh1, Rdh7, REL, RELB, REV3L, RIPK2, S100A10, S100A4, S100A6, SAA1, SAA2, SAA, SAT1, SCNN1A, SDC4, SELE, SELP, SELS, SENP2, SERPINA1, SERPINA2, SERPINA3, SERPINB1, SERPINE1, PAI-1, SERPINE2, SH3BGRL, SKALP, PI3, SKP2, SLC11A2, SLC16A1, SLC3A2, SLC6A6, Slfn2, SNAI1, SOD1, SOD2, SOX9, SPATA19, SPI1, SPP1, ST6GAL1, ST8SIA1, STAT5A, SUPV3L1, TACR1, TAP1, TAPBP, TCRB, TERT, TF, TFEC, TFF3, TFPI2, TGM1, TGM2, THBS1, THBS2, TICAM1, TIFA, TLR2, TLR9, TNC, TN, TNFAIP2, TNFAIP3, TNFRSF1B, TNFRSF4, TNFRSF9, TNFSF10, TNFSF13B, TNFSF13B, TNFSF15, TNIP1, TNIP3, TP53, TRAF1, TRAF2, TREM1, TRPC1, TWIST1, UBE2M, UCP2, UGCGL1, UPK1B, UPP1, VCAM1, VEGFC, VIM, VPS53, WNT10B, WT1, XDH, XIAP, YY1, and ZNF366.

55. The method of any one of claims 51 to 54, wherein Compound 8 decreases the expression of one or more NFκB-associated genes in the subject, and / or increases the expression of one or more NFκB-associated genes in the subject.

56. The method of any one of claims 51 to 54, wherein Compound 8 decreases the expression of one or more NFκB-associated genes found to be elevated in the subject, and / or increases the expression of one or more NFκB-associated genes found to be decreased in the subject.

57. The method of claim 55 or 56, wherein Compound 8 decreases the expression of one or more NFκB-associated genes found to be elevated in the subject before the administration of Compound 8, and / or increases the expression of one or more NFκB-associated genes found to be decreased in the subject before the administration of Compound 8. DB1 / 147901903.2 35558. The method of any one of claims 55 to 57, wherein Compound 8 decreases the expression of one or more NFκB-associated genes found to be elevated in the subject compared to a healthy control subject, and / or increases the expression of one or more NFκB-associated genes found to be decreased in the subject compared to a healthy control subject.

59. The method of any one of claims 55 to 58, wherein Compound 8 decreases the expression of one or more NFκB-associated genes selected from: A4, ABCA1, ABCB1, ABCB4, ABCB9, ABCC6, ABCG5, ABCG8, ADAM19, ADH1A, ADORA1, ADORA2A, ADRA2B. AFP, AGER, AGT, AHCTF1, AICDA, AKR1C1, ALOX12, ALOX5, AMACR, AMH, ANGPT1, APOBEC2, APOC3, APOD, APOE, AQP4, AR, ARFRP1, ART1, ASPH, ASS1, ATP1A2, B2M, BACE1, BAX, BCL2, BCL2A1, BCL2L1, BCL2L11, BCL3, BDKRB1, BDKRB1, BDNF, BGN, BLIMP1 / PRDM1, BLNK, BLR1, BMI1, BMP2, BMP4, BNIP3, BRCA2, BTK, C3, C4A, C4BPA, C69, CALCB, CASP4, CAV1, CCL1, CCL15, CCL17, CCL19, CCL2, CCL20, CCL22, CCL23, CCL28, CCL3, CCL4, CCL5, CCND1, CCND2, CCND3, CCR5, CCR7, CD209, CD274, CD38, CD3G, CD40, CD40LG, CD44, CD48, CD54, CD80, CD83, CD86, CDK6, CDKN1A, CDX1, CEBPD, CFB, CFLAR, CGM3, CHI3L1, CIDEA, CLDN2, COL1A2, CR2, CREB3, CRP, CSF1, CSF2, CSF3, CTSB, CTSL1, CXCL1, CXCL10, CXCL11, CXCL3, CXCL5, CXCL6, CXCL9, CYP19A1, CYP27B1, CYP2C11, CYP2E1, CYP7B1, DCTN4, DEFB2, DIO2, DMP1, DNASE1L2, DPYD, DUSP1, E2F3, EBI3, EDN1, EGFR, EGR1, ELF3, ENG, ENO2, EPHA1, EPO, ERBB2, ERVWE1, F11R, F3, F8, FABP6, FAM148A, FAS, FASLG, FCER2. FCER2 / CD23, FCGRT, FGF8, FN1, FOS, FSTL3, FTH1, G6PC, G6PD, GAD1, GADD45B, GATA3, GBP1, GCLC, GCLM, GCNT1, GJB1, GNAI2, GNB2L1, GNRH2, GRIN1, GRIN2A, GRM2, GRO-beta, GRO-gamma, GSTP1, GUCY1A2, GZMB, HAMP, HAS1, HBE1, HBZ, HGF, HIF1A, HLA-B, HLA-G, HMGN1, HMOX1, HOXA9, HPSE, HSD11B2, HSD17B8, HSP90AA1, ICOS, IDO1, IER2, IER3, IFI44L, IFNB, IFNG, IGFBP1, IGFBP2, IGHE, IGHG1, IGHG2, IGHG4, IGKC, Iigp1, IL10, IL11, IL12A, IL12B, IL13, IL15, IL17, IL1A, IL1B, IL1RN, IL2, IL23A, IL27, IL2RA, IL6, IL8, IL8RA, IL8RB, IL9, INHBA, IRF1, IRF2, IRF4, IRF7, JMJD3, JUNB, KC, KCNK5, KCNN2, KISS1, KITLG, KLF10, KLK3, KLRA1, KRT15, KRT3, KRT5, KRT6B, LAMB2, LBP, LCN2, LEF1, LGALS3, LIPG, LTA, LTB, LTF, LYZ, MADCAM1, MAP4K1, MBP, MDK, MMP1, MMP3, MMP9, MT3, MTHFR, MUC2, MX1, MYB, MYC, MYLK, MYOZ1, DB1 / 147901903.2 356NCAM, NFKB1, NFKB2, NFKBIA, NFKBIE, NFKBIZ, NGFB, NK4, NLRP2, NOD2, NOS1, NOS2A, NOX1, NPY1R, NQO1, NR3C1, NR4A2, NRG1, NUAK2, OLR1, OPN1SW, OPRD1, OPRM1, ORM1, Osterix, OXTR, PAFAH2, PAX8, PDE7A, PDGFB, PDYN, PENK, PGK1, PGLYRP1, PGR, PI3KAP1, PIGF, pIgR, PIK3CA, PIM1, PLA2, PLAU, PLCD1, PLK3, POMC, PPARGC1B, PPP5C, PRF1, PRKACA, PRKCD, PRL, PSMB9, PSME1, PSME2, PTAFR,, PTEN, PTGDS, PTGES, PTGIS, PTGS2, PTHLH, PTPN1, PTPN13, PTS, PTX3, PYCARD, RAG1, RAG2, RBBP4, Rdh1, Rdh7, REL, RELB, REV3L, RIPK2, S100A10, S100A4, S100A6, SAA1, SAA2, SAA, SAT1, SCNN1A, SDC4, SELE, SELP, SELS, SENP2, SERPINA1, SERPINA2, SERPINA3, SERPINB1, SERPINE1, PAI-1, SERPINE2, SH3BGRL, SKALP, PI3, SKP2, SLC11A2, SLC16A1, SLC3A2, SLC6A6, Slfn2, SNAI1, SOD1, SOD2, SOX9, SPATA19, SPI1, SPP1, ST6GAL1, ST8SIA1, STAT5A, SUPV3L1, TACR1, TAP1, TAPBP, TCRB, TERT, TF, TFEC, TFF3, TFPI2, TGM1, TGM2, THBS1, THBS2, TICAM1, TIFA, TLR2, TLR9, TNC, TN, TNFAIP2, TNFAIP3, TNFRSF1B, TNFRSF4, TNFRSF9, TNFSF10, TNFSF13B, TNFSF13B, TNFSF15, TNIP1, TNIP3, TP53, TRAF1, TRAF2, TREM1, TRPC1, TWIST1, UBE2M, UCP2, UGCGL1, UPK1B, UPP1, VCAM1, VEGFC, VIM, VPS53, WNT10B, WT1, XDH, XIAP, YY1, and ZNF366 in the subject.

60. The method of any one of claims 55 to 58, wherein Compound 8 increases the expression of one or more NFκB-associated genes selected from: A4, ABCA1, ABCB1, ABCB4, ABCB9, ABCC6, ABCG5, ABCG8, ADAM19, ADH1A, ADORA1, ADORA2A, ADRA2B. AFP, AGER, AGT, AHCTF1, AICDA, AKR1C1, ALOX12, ALOX5, AMACR, AMH, ANGPT1, APOBEC2, APOC3, APOD, APOE, AQP4, AR, ARFRP1, ART1, ASPH, ASS1, ATP1A2, B2M, BACE1, BAX, BCL2, BCL2A1, BCL2L1, BCL2L11, BCL3, BDKRB1, BDKRB1, BDNF, BGN, BLIMP1 / PRDM1, BLNK, BLR1, BMI1, BMP2, BMP4, BNIP3, BRCA2, BTK, C3, C4A, C4BPA, C69, CALCB, CASP4, CAV1, CCL1, CCL15, CCL17, CCL19, CCL2, CCL20, CCL22, CCL23, CCL28, CCL3, CCL4, CCL5, CCND1, CCND2, CCND3, CCR5, CCR7, CD209, CD274, CD38, CD3G, CD40, CD40LG, CD44, CD48, CD54, CD80, CD83, CD86, CDK6, CDKN1A, CDX1, CEBPD, CFB, CFLAR, CGM3, CHI3L1, CIDEA, CLDN2, COL1A2, CR2, CREB3, CRP, CSF1, CSF2, CSF3, CTSB, CTSL1, CXCL1, CXCL10, CXCL11, CXCL3, CXCL5, CXCL6, CXCL9, CYP19A1, CYP27B1, CYP2C11, CYP2E1, CYP7B1, DCTN4, DEFB2, DIO2, DMP1, DNASE1L2, DPYD, DUSP1, E2F3, EBI3, DB1 / 147901903.2 357EDN1, EGFR, EGR1, ELF3, ENG, ENO2, EPHA1, EPO, ERBB2, ERVWE1, F11R, F3, F8, FABP6, FAM148A, FAS, FASLG, FCER2. FCER2 / CD23, FCGRT, FGF8, FN1, FOS, FSTL3, FTH1, G6PC, G6PD, GAD1, GADD45B, GATA3, GBP1, GCLC, GCLM, GCNT1, GJB1, GNAI2, GNB2L1, GNRH2, GRIN1, GRIN2A, GRM2, GRO-beta, GRO-gamma, GSTP1, GUCY1A2, GZMB, HAMP, HAS1, HBE1, HBZ, HGF, HIF1A, HLA-B, HLA-G, HMGN1, HMOX1, HOXA9, HPSE, HSD11B2, HSD17B8, HSP90AA1, ICOS, IDO1, IER2, IER3, IFI44L, IFNB, IFNG, IGFBP1, IGFBP2, IGHE, IGHG1, IGHG2, IGHG4, IGKC, Iigp1, IL10, IL11, IL12A, IL12B, IL13, IL15, IL17, IL1A, IL1B, IL1RN, IL2, IL23A, IL27, IL2RA, IL6, IL8, IL8RA, IL8RB, IL9, INHBA, IRF1, IRF2, IRF4, IRF7, JMJD3, JUNB, KC, KCNK5, KCNN2, KISS1, KITLG, KLF10, KLK3, KLRA1, KRT15, KRT3, KRT5, KRT6B, LAMB2, LBP, LCN2, LEF1, LGALS3, LIPG, LTA, LTB, LTF, LYZ, MADCAM1, MAP4K1, MBP, MDK, MMP1, MMP3, MMP9, MT3, MTHFR, MUC2, MX1, MYB, MYC, MYLK, MYOZ1, NCAM, NFKB1, NFKB2, NFKBIA, NFKBIE, NFKBIZ, NGFB, NK4, NLRP2, NOD2, NOS1, NOS2A, NOX1, NPY1R, NQO1, NR3C1, NR4A2, NRG1, NUAK2, OLR1, OPN1SW, OPRD1, OPRM1, ORM1, Osterix, OXTR, PAFAH2, PAX8, PDE7A, PDGFB, PDYN, PENK, PGK1, PGLYRP1, PGR, PI3KAP1, PIGF, pIgR, PIK3CA, PIM1, PLA2, PLAU, PLCD1, PLK3, POMC, PPARGC1B, PPP5C, PRF1, PRKACA, PRKCD, PRL, PSMB9, PSME1, PSME2, PTAFR,, PTEN, PTGDS, PTGES, PTGIS, PTGS2, PTHLH, PTPN1, PTPN13, PTS, PTX3, PYCARD, RAG1, RAG2, RBBP4, Rdh1, Rdh7, REL, RELB, REV3L, RIPK2, S100A10, S100A4, S100A6, SAA1, SAA2, SAA, SAT1, SCNN1A, SDC4, SELE, SELP, SELS, SENP2, SERPINA1, SERPINA2, SERPINA3, SERPINB1, SERPINE1, PAI-1, SERPINE2, SH3BGRL, SKALP, PI3, SKP2, SLC11A2, SLC16A1, SLC3A2, SLC6A6, Slfn2, SNAI1, SOD1, SOD2, SOX9, SPATA19, SPI1, SPP1, ST6GAL1, ST8SIA1, STAT5A, SUPV3L1, TACR1, TAP1, TAPBP, TCRB, TERT, TF, TFEC, TFF3, TFPI2, TGM1, TGM2, THBS1, THBS2, TICAM1, TIFA, TLR2, TLR9, TNC, TN, TNFAIP2, TNFAIP3, TNFRSF1B, TNFRSF4, TNFRSF9, TNFSF10, TNFSF13B, TNFSF13B, TNFSF15, TNIP1, TNIP3, TP53, TRAF1, TRAF2, TREM1, TRPC1, TWIST1, UBE2M, UCP2, UGCGL1, UPK1B, UPP1, VCAM1, VEGFC, VIM, VPS53, WNT10B, WT1, XDH, XIAP, YY1, and ZNF366 in the subject.

61. A method of determining whether a subject with a disease or disorder selected from an inflammatory disease or disorder, or a cancer selected from acute myeloid leukemia (AML) DB1 / 147901903.2 358and myelodysplastic syndrome (MDS), can be treated by the administration of Compound 8 or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, the method comprising: determining whether the subject has an elevated secretion of one or more cytokines selected from: TNF-α, IL-1 β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, IL-23, GM- CSF, and IFN-γ.

62. The method of claim 61, wherein the subject has elevated expression of one or more cytokines compared to a healthy control subject and / or a decreased expression of one or more cytokines compared to a healthy control subject.

63. The method of any one of claims 41 to 62, further comprising administering to the subject Compound 8: or a salt, ester, solvate, opticalof an isomer thereof.

64. The method of any one of claims 41 to 63, wherein the inflammatory disease or disorder is selected from chronic inflammation, sepsis, rheumatoid arthritis, hidradenitis suppurativa, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, psoriasis, Sjögren’s syndrome, Ankylosing spondylitis, systemic sclerosis, Type 1 diabetes mellitus, Crohn’s disease, atopic dermatitis, and colitis.

65. The method of any one of claims 41 to 63, wherein: the AML is relapsed AML, refractory AML, relapsed / refractory AML, AML with resistance to hypomethylating agents, AML with resistance to venetoclax, AML with resistance to hypomethylating agents and venetoclax, monocytic AML, or monocytic-like AML, optionally DB1 / 147901903.2 359wherein the subject has AML and the subject has a gene mutation in one or more of FLT3, TET2, KIT, BCOR, BRAF, CDKN2A, UTX, ZRSR2, NPM1, PTEN, DNMT3A, EZH2, RUNX1, JAK2, ASXL1, ABL1, ATRX, BCORL1, KDM6A, PTPN11, TP53, CBL, CEBPA, FBXW7, HRAS, NRAS, IDH1, IDH2, NRAS, PDGFRA, SF3B1, ETV6, PHF6, GNAS, KRAS, NOTCH1, STAG2, SETBP1, GATA1, GATA2, WT1, SRSF2, GNAS, CEBPA, CALR, MPL, BCL11A, ATM, CTCF, U2AF1, TYK2, FBX, RUI, RAD21, or MLL3; and / or the MDS is MDS with a splicing factor mutation, MDS with a mutation in isocitrate dehydrogenase 1, or MDS with a mutation in isocitrate dehydrogenase 2, optionally wherein the subject has MDS and has a gene mutation in U2AF1, FLT3, ASXL1, BCORL1, BRAF, CBL, CDKN2A, DNMT3A, FBXW7, GATA2, IDH2, KRAS, NOTCH1, NRAS, PDGFRA, PTEN, PTPN11, TET2, TP53, EZH2, HRAS, KIT, MPL, PHF6, RUNX1, WT1, ABL1, CEBPA, ETV6, IDH2, KDM6A, KIT, KRAS, PTEN, RUNX1, SF3B1, or ZRSR2; and / or optionally wherein the MDS with a splicing factor mutation comprises MDS with a splicing factor mutation in U2AF1, SRSF2, SF3B1, or ZRSR2.

66. The method of any one of claims 41 to 65, wherein Compound 8 has an IRAK1 IC50of less than about 40 nM, optionally an IRAK4 IC50of less than about 5 nM, and / or an FLT3 IC50 of less than about 2.5 nM.

67. The method of any one of claims 41 to 66, wherein Compound 8 has IRAK4:IRAK1 inhibitory potency ratio of less than about 40.

68. The method of any one of claims 41 to 67, wherein Compound 8 is more effective at inhibiting cancer cell colony formation and / or cancer progenitor cell function when compared to a compound which inhibits IRAK1 without inhibiting IRAK4 or inhibits IRAK4 without inhibiting IRAK1.

69. The method of any one of claims 41 to 68, wherein Compound 8 provides sustained treatment of the inflammatory disease / disorder, AML, or MDS in the subject, optionally wherein the sustained treatment is greater than the treatment provided from a compound which inhibits IRAK1 without inhibiting IRAK4 or inhibits IRAK4 without inhibiting IRAK1. DB1 / 147901903.2 36070. The method of any one of claims 41 to 69, wherein: the administration comprises parenteral administration, mucosal administration, intravenous administration, subcutaneous administration, topical administration, intradermal administration, oral administration, sublingual administration, intranasal administration, or intramuscular administration; and / or Compound 8 is administered to the subject in an amount of from about 0.005 mg / kg subject body weight to about 1,000 mg / kg subject body weight; and / or Compound 8 is administered to the subject in a dosage of from about 0.35 mg to about 70,000 mg; and / or Compound 8 is administered to the subject daily, every other day, every third day, every fourth day, every fifth day, every sixth day, once a week, twice a month, or once a month.

71. The method of any one of claims 41 to 70, wherein Compound 8 treats the inflammatory disease or disorder, or the cancer selected from AML and MDS, in the subject during the time period that the compound is administered to the subject.

72. The method of any one of claims 41 to 71, wherein Compound 8 continues to treat the inflammatory disease or disorder, or the cancer selected from AML and MDS, in the subject after the administration is stopped, optionally wherein Compound 8 continues to treat the inflammatory disease or disorder, or the cancer selected from AML and MDS, in the subject for about 1 day, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, about one week, about two weeks, about three weeks, or about a month after the administration is stopped.

73. The method of any one of claims 41 to 72, further comprising administering to the subject one or more of: a chemotherapy agent, a BCL2 inhibitor, an immune modulator, a BTK inhibitor, a DNA methyltransferase inhibitor / hypomethylating agent, an anthracycline, a histone deacetylase (HDAC) inhibitor, a purine nucleoside analogue (antimetabolite), an isocitrate dehydrogenase 1 or 2 (IDH1 and / or IDH2) inhibitor, an antibody-drug conjugate, an mAbs / immunotherapy, a Plk inhibitor, a MEK inhibitor, a CDK inhibitor, a CDK9 inhibitor, a CDK8 inhibitor, a retinoic acid receptor agonist, a TP53 activator, a CELMoD, a smoothened receptor antagonist, an ERK inhibitor including an ERK2 / MAPK1 or ERK1 / MAPK3 inhibitor, DB1 / 147901903.2 361a PI3K inhibitor, an mTOR inhibitor, a steroid or glucocorticoid, a steroid or glucocorticoid receptor modulator, an EZH2 inhibitor, a hedgehog (Hh) inhibitor, a Topoisomerase I inhibitor, a Topoisomerase II inhibitor, an aminopeptidase / Leukotriene A4 hydrolase inhibitor, a FLT3 / Axl / ALK inhibitor, a FLT3 / KIT / PDGFR, PKC, and / or KDR inhibitor, a Syk inhibitor, an E-selectin inhibitor, an NEDD8-activator, an MDM2 inhibitor, a PLK1 inhibitor, an Aura A inhibitor, an aurora kinase inhibitor, an EGFR inhibitor, an AuroraB / C / VEGFR1 / 2 / 3 / FLT3 / CSF- 1R / Kit / PDGFRA / B inhibitor, an AKT 1, 2, and / or 3 inhibitor, a ABL1 / 2 / SRC / EPHA2 / LCK / YES1 / KIT / PDGFRB / FYN inhibitor, a farnesyltransferase inhibitor, a BRAF / MAP2K1 / MAP2K2 inhibitor, a Menin-KMT2A / MLL inhibitor, and a multikinase inhibitor; optionally comprising administering to the subject at least one of a BCL2 inhibitor, a BTK inhibitor, a glucocorticoid, a CDK inhibitor, and a DNA methyltransferase inhibitor.

74. The method of claim 73, wherein: the BCL2 inhibitor is venetoclax or a pharmaceutically acceptable salt thereof; and / or the BTK inhibitor is ibrutinib or acalabrutinib or a pharmaceutically acceptable salt of any one thereof; and / or the glucocorticoid is selected from dexamethasone, methylprednisolone, prednisolone or a pharmaceutically acceptable salt of any one thereof; and / or the CDK inhibitor is selected from CDK4 / 6 inhibitor Palbociclib, CDK7 inhibitor THZ1, and / or CDK9 inhibitors BAY1251152 and Atuveciclib, or a pharmaceutically acceptable salt of any one thereof; and / or the DNA methyltransferase inhibitor is azacitidine or a pharmaceutically acceptable salt thereof.

75. The method of claim 73 or 74, wherein the combination of Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, and venetoclax, or a pharmaceutically acceptable salt thereof, increases survival of the subject; optionally wherein the combination of Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, and venetoclax, or a pharmaceutically acceptable salt thereof, increases survival of the subject compared to a subject administered either Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, or venetoclax, or a DB1 / 147901903.2 362pharmaceutically acceptable salt thereof; optionally wherein the combination of Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, and venetoclax, or a pharmaceutically acceptable salt thereof, increases survival of the subject by about 10% to 200%, about 10% to 175%, about 20% to 175%, or about 20% to 150% compared to the subject administered either Compound 8, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof, or venetoclax, or a pharmaceutically acceptable salt thereof. DB1 / 147901903.2 363

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