Peptide inhibitors of trim7 and uses thereof

Abstract

The present disclosure relates to compositions and methods, including Trim / inhibitors that find use in the treatment of disease, such as therapies for cancer, including cancers that are resistant to anti-checkpoint agents, infectious diseases and inflammatory diseases.

Description

FIELD OF THE DISCLOSURE The present disclosure relates to, inter alia, compositions and methods, including compounds including Trim7 inhibitors that find use in the treatment of disease, such as therapies for cancer, including cancers that are resistant to anticheckpoint agents, infectious diseases and inflammatory diseases. CROSS-REFERENCE TO RELATED APPLICATIONS The present International application claims priority to U.S. Provisional Patent Application No. 63 / 561,071, filed March 4, 2024, U.S. Provisional Patent Application No. 63 / 631,148, filed April 8, 2024, and U.S. Provisional Patent Application No. 63 / 684,401, filed on August 18, 2024, each of which is incorporated by reference herein in its entirety. SEQUENCE LISTING The instant application contains a sequence listing, which has been submitted in XML format via EFS-Web. The contents of the XML copy named “SHK-084PC_116981-5084_Sequence_Listing.xml” which was created on February 28, 2025, and is 19,676 bytes in size, are incorporated herein by reference in their entirety. BACKGROUND Drug resistance remains one of the biggest challenges in cancer therapy. Drug resistance is found across all types of cancer and all modes of treatment, including molecularly targeted therapy, immunotherapy, and chemotherapy. In some patients, initiation of efficacious therapy is delayed by the inability to predict responses. Moreover, it is also common that a patient with advanced cancer receives a drug that helps shrink their tumors, but then the cancer develops resistance to the drug. Unfortunately, few effective therapeutic options are available for some patients having cancers that are resistant to the anti-checkpoint therapies. Therefore, methods for developing new therapies for patients suffering from drug resistant cancer are required for improving outcomes in cancer patients. SUMMARY Accordingly, the present disclosure provides, in part, compositions and methods for treating cancer, including, without limitations, cancers that are resistant to anti-checkpoint agents. Also provided are methods for treating infectious diseases and inflammatory diseases. Also provided are methods for selecting patients for cancer treatment, and methods for cancer treatment, based on, for instance, based on gene expression profiles of Trim7, which is dysregulated in anti-checkpoint resistant cancers. in one aspect, the present disclosure relates to a compound of the formula (I): L1-(([Aaa]w)n-[Aaa]x-[Aaa]y-[Aaa]z-Ter)-L2. In embodiments, L1 and / or L2 are independently present or absent; and L1 and / or L2, if present, are each independently selected from a carrier protein, a tag, and a chemical group, the chemical group is optionally selected from acryloyl, amino, alkyl, acyl group, a glycosyl moiety, and a polymer. In embodiments, each [Aaa]w is independently selected from an amino acid. In embodiments, n = 0-20. In embodiments, [Aaa]x is absent or is an amino acid. In embodiments, [Aaa]yis absent or is an amino acid. In embodiments, [Aaa]zis an hydrophobic or aromatic amino acid; and Ter is Gin or Asn. In embodiments, Ter is Gin. In embodiments, [Aaa]zis an aromatic amino acid selected from Tyr, Trp, Phe, and 3-methyl-Phe. In embodiments, the nitrogen of the aromatic amino acid is substituted with an alkyl group. In embodiments, the nitrogen of the aromatic amino acid is (e.g. Tyr, Trp, Phe, and 3-methyl-Phe) substituted with a methyl group. In embodiments, [Aaa]zis Phe or 3-methyl-Phe. In embodiments, [Aaa]z is a hydrophobic amino acid selected from Leu, Vai, lie, Ala, 3-(pyridin-4-yl)-Ala and 3-(pyridin-3-yl)-Ala. In embodiments, [Aaa]z is Leu, 3-(pyridin-4-yl)-Ala or 3-(pyridin-3-yl)-Ala. In embodiments, [Aaa]zis Met. In embodiments, [Aaa]x and / or [Aaa]y is present and each isindependently a natural amino acid. In embodiments, [Aaa]y is present and is a nonpolar amino acid, aromatic amino acid or a polar amino acid. In embodiments, [Aaa]y is a nonpolar amino acid selected from Vai, Gly, Ala, Leu, Met, Trp, Phe, lie, and Pro or an analogue thereof, optionally wherein Pro analogue is selected from (R)-p-Pro and (S)-p-Pro, optionally wherein Ala analogue is 3-(4-pyridyl)-L-alanine, optionally wherein Pro is (R)-Pro or (S)-Pro, wherein the alpha carbon of the Pro is optionally substituted with an alkyl group, optionally a methyl group (e.g. a-methyl-L-proline), optionally wherein the alpha carbon of the Gly is substituted with an alkyl or cyloalkyl group, optionally a cyclopropyl group (e.g. a-cyclopropane-Gly), optionally wherein the beta carbon of the Ala is substituted with a aryl or heteroaryl, optionally a pyridine group. In embodiments, [Aaa]y is selected from Leu, Pro, (R)-p-Pro, (S)-p-Pro, Trp , (R)-Pro, (S)-Pro, 3-(4-pyridyl)-L-alanine, and a-cyclopropane-Gly, wherein the alpha carbon of the Pro is optionally substituted with an alkyl group, optionally a methyl group (e.g. a-methyl-L-proline). In embodiments, [Aaa]yis a polar amino acid selected from Ser, Thr, Gin and Asn. In embodiments, the polar amino acid is a charged amino acid selected from Lys, Arg, His, Glu and Asp. In embodiments, [Aaa]y is an aromatic amino acid selected from Tyr, Trp and Phe. In embodiments, [Aaa]yis Tyr. In embodiments, [Aaa]yis a hydrophobic amino acid selected from Vai, Leu, and lie. In embodiments, [Aaa]yis Leu. In embodiments, [Aaa]x is present and is a nonpolar amino acid, aromatic amino acid or a polar amino acid. In embodiments, [Aaa]xis a nonpolar amino acid selected from Vai, Gly, Ala, Leu, Met, Trp, Phe, lie, and Pro or an analogue of any one thereof, optionally wherein Pro is (R)-p-Pro or (S)-p-Pro. In embodiments, [Aaa]x is Ala. In embodiments, [Aaa]xis (R)-|3-Pro. In embodiments, [Aaa]xis (S)-|3-Pro. In embodiments, [Aaa]xis an aromatic amino acid selected from Tyr, Trp and Phe. In embodiments, [Aaa]xis Phe. In embodiments, [Aaa]xis a polar amino acid selected from Ser, Thr, Gin and Asn. In embodiments, [Aaa]x is Thr. In embodiments, the compound comprises at least one, or at least two, or at least three, or at least 4, or at least 5, or at least 6, or at least 7, or at least 8, or at least 9 or at least 10, or at least 15, or more [Aaa]„. In embodiments, each [Aaa]w each is independently a natural amino acid. In embodiments, each [Aaa]w is independently selected from a nonpolar amino acid, aromatic amino acid or a polar amino acid. In embodiments, n is 0 and [Aaa]wis absent. In embodiments, L1 is present and is acryloyl or an acyl group, optionally wherein the acyl group is CH3-CH2-C(O)-, CH3-C(O)-, or CH3-C=C-C(0)-. In embodiments, L2 is present and is amino or -OCH3. In embodiments, one or more of [Aaa]w, [Aaa]xand [Aaa]yare present and are independently naturally modified amino acids or non-standard amino acids. In embodiments, the naturally modified amino acids or non-standard amino acids are one or more of 4-hydroxyproline and 5-hydroxylysine, and glycosylated amino acids. In embodiments, L1 and / or L2 is or comprises a carrier protein selected from Fc domain, albumin, transferrin, or elastinlike protein, Keyhole Limpet Hemocyanin (KLH), ovalbulin, or a variant thereof. In embodiments, the carrier protein comprises a Fc domain selected from an IgG Fc domain, an IgA Fc domain, an IgM Fc domain, an IgE Fc domain, and an IgD Fc domain. In embodiments, the carrier protein comprises an IgG Fc domain the IgG Fc domain is selected from an lgG1 Fc domain, an lgG2 Fc domain, an lgG3 Fc domain, and an lgG4 Fc domain. In embodiments, the carrier protein comprises an IgA Fc domain selected from an lgA1 Fc domain and an lgA2 Fc domain. In embodiments, the carrier protein is linked at the N-terminus of ([Aaa]w)n-[Aaa]x-[Aaa]y-[Aaa]z-Ter). In embodiments, the carrier protein is linked at the C-terminus of ([Aaa]w)n-[Aaa]x-[Aaa]y-[Aaa]z-Ter). In embodiments, the carrier protein is linked to ([Aaa]w)n-[Aaa]x-[Aaa]y-[Aaa]z-Ter) via a peptide linker. In embodiments, the peptide linker is rigid or flexible. In embodiments, L1 and / or L2 comprises or further comprises a tag. In embodiments, the tag is selected from hexahistidine tag, FLAG tag, Strep II tag, streptavidin-binding peptide (SBP) tag, calmodulin-binding peptide (CBP), glutathione S-transferase (GST), maltose-binding protein (MBP), S-tag, HA tag, and c-Myc tag. In embodiments, L1 and / or L2 comprises or further comprises a glycosyl moiety. In embodiments, the glycosyl moiety is an N-linked glycosyl moiety. In embodiments, the glycosyl moiety is an O-linked glycosyl moiety. In embodiments, the compound comprises one or more N-linked glycosylation consensus sites and / or O-linked glycosylation consensus sites. In embodiments, the compound is biosynthesized as a single polypeptide chain. In embodiments, the compound is biosynthesized from a single open reading frame. In embodiments, the compound is prepared using an expression system. In embodiments, the expression system is selected from bacterial, yeast, invertebrate (e.g., an insect cell), vertebrate (e.g, a mammalian cell), and plant expression system. In embodiments, one or more of [Aaa]w, [Aaa]x and [Aaa]y are present and are independently selected from non-natural amino acids (e.g., D-amino acids (Daa), and those comprising N-methylation (Nm), Ca-methylation (Cm), amino isobutyric acids (Aib), ^(CFbNH) reduced amide bonds (Rd), and peptoids (Pp)). In embodiments, L1 and / or L2 comprises or further comprises an alkyl or acyl group that is conjugated to the compound, optionally wherein the acyl group is CH3-CH2-C(O)-, CH3-C(0)-, or CH3-C=C-C(O)-. In embodiments, L comprises an acyl group, optionally wherein the acyl group is CH3-CH2-C(O)-, CH3-C(0)-, or CH3-C=C-C(0)-. In embodiments, the acyl group is an acetyl group. In embodiments, L1 and / or L2 comprises or further comprises a polymer. In embodiments, the polymer is selected from poly(alkylene oxide) (e.g., polyethylene glycol (PEG)), poly(N-vinylpyrrolidone), poly(vinyl alcohol), poly (glycerol), poly(zwitterions), poly(carbonates), polyoxazoline, poly(acryloylmorpholine), poly(oxazolines), poly(sacharrides), and a combination thereof. In embodiments, the polymer is a polyethylene glycol (PEG). In embodiments, one or more amino acids present in the present in ([Aaa]w)n-[Aaa]x-[Aaa]y-[Aaa]z-Ter), the carrier protein, or the tag are PEGylated. In embodiments, one or more PEGylated amino acids comprises Lys and PEGylation is conducted via amine conjugation. In embodiments, one or more PEGylated amino acids comprises Gin and PEGylation is conducted via transglutaminase (TGase) mediated enzymatic conjugation. In embodiments, one or more PEGylated amino acids comprises Cys and PEGylation is conducted via thiol conjugation. In embodiments, the compound of formula (I) is selected from L1-Phe-Gln, L1-Leu-Phe-Gln, L1-Leu-Phe-Gln-L2, L1-Leu-3-methyl-Phe-Gln, L1-(R)-P-Pro-Phe-Gln, and L1-(S)-|3-Pro-Phe-Gln, optionally wherein L1 is an acyl group or acryloyl and optionally wherein L2 is amino. In embodiments, the compound is a compound of formula(ll), a stereoisomer, or a pharmaceutically acceptable salt thereof: Formula (II) wherein: R1a, and R1b are at each occurrence independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted 5 heteroarylalkyl; R2 is selected from hydrogen, unsubstituted or substituted alkyl, and unsubstituted or substituted alkylaryl; v ■ i t j f ru ru p5                O R®a         j R® X is selected from -CH=CH2, r<              , U IX , and tx                    ; Y is selected from -0R3a, and -NR3bR3c; R3a, R3b and R3c are at each occurrence independently selected from hydrogen, unsubstituted or substituted 10 alkyl, unsubstituted or substituted alkylaryl, and unsubstituted or substituted aryl; optionally wherein R3b and R3c are joined to form an optionally substituted cycloalkyl; R4a and R4b are at each occurrence independently selected from hydrogen, unsubstituted or substituted alkyl, and unsubstituted or substituted alkylaryl, optionally wherein R4a and R4b are joined to form an optionally substituted cycloalkyl; R5 is selected from unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted aryl, and unsubstituted or substituted alkylaryl; R6 is selected from hydrogen, unsubstituted or substituted alkyl, and unsubstituted or substituted alkylaryl; R7 is selected from unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted aryl, and unsubstituted or substituted alkylaryl; R8a and R8b are at each occurrence independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl, optionally wherein R8a and R8b are joined to form an optionally substituted cycloalkyl; R9 is selected from unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted aryl, and unsubstituted or substituted alkylaryl; and R10 is selected from hydrogen, unsubstituted or substituted alkyl, and unsubstituted or substituted alkylaryl. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein Y is selected from -OH, OCH3, NH2, NHMe, and NMe2. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R1a is hydrogen and R1b is selected from: wherein R11 is selected from hydrogen, unsubstituted or substituted alkyl, and unsubstituted or substituted alkylaryl. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R11 is methyl. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R1a and R1b are at each occurrence independently selected from: In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R4a and R4b are at each occurrence independently selected from hydrogen, methyl, isopropyl, and isobutyl. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R2 is selected from hydrogen, methyl, isopropyl, and isobutyl. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R2 is selected from hydrogen and methyl. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R5 is selected from -CH=CH2, -CH2-CH3, and -C^CCHs. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R6 is selected from hydrogen, and methyl. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R7 is selected from -CH3, -CH=CH2, -CH2-CH3, and -0=001¼ 5 In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R8a is hydrogen, and R8b is selected from hydrogen, methyl, isopropyl, and isobutyl. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R8a and R8b are joined to form an optionally substituted cycloalkyl; optionally R8a and R8b are joined to form cyclopropyl. 10 In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R9 is selected from -CH=CH2, -CH2-CH3, and -C=CCH3. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R10 is selected from hydrogen and methyl. In embodiments, the compound is a compound of formula (Ila), a stereoisomer, or a pharmaceutically acceptable salt 15 thereof: Formula (Ila). In embodiments, the compound is a compound of formula (lib), a stereoisomer, or a pharmaceutically acceptable salt thereof: Formula (lib). In embodiments, the compound is a compound of formula (lie), a stereoisomer, or a pharmaceutically acceptable salt thereof: Formula (lie). In embodiments, the compound is a compound of formula (Illa), a stereoisomer, or a pharmaceutically acceptable salt thereof: 10 Formula (Illa). In embodiments, the compound is a compound of formula (lllb), a stereoisomer, or a pharmaceutically acceptable salt thereof: Formula (lllb). In some embodiments, the compound is a compound of formula (Ila), (lib), (lie), (Illa), (lllb), a stereoisomer, or a pharmaceutically acceptable salt of any one thereof, wherein R1b is selected from: In some embodiments, the compound is a compound of formula (Ila), (lib), (lie), (Illa), (lllb), a stereoisomer, or a pharmaceutically acceptable salt of any one thereof, wherein R2 is selected from hydrogen and methyl. In some embodiments, the compound is a compound of formula (Ila), (lib), (He), (Illa), (lllb), a stereoisomer, or a pharmaceutically acceptable salt of any one thereof, wherein X is selected from -CH=CH2, In some embodiments, the compound is a compound of formula (Ila), (lib), (He), (Illa), (lllb), a stereoisomer, or a pharmaceutically acceptable salt of any one thereof, wherein R4a and R4b are at each occurrence independently selected from hydrogen and methyl. In some embodiments, the compound is a compound of formula (Illa), (lllb), a stereoisomer, or a pharmaceutically acceptable salt of any one thereof, wherein R8b is isobutyl. In some embodiments, the compound is a compound of formula (Ila), (lib), (He), (Illa), (lllb), a stereoisomer, or a pharmaceutically acceptable salt of any one thereof, wherein R7 is selected from -CH3, -CH=CH2, -CH2-CH3, and -C=CCH3. In some embodiments, the compound is a compound of formula (Ha), (lib), (lie), a stereoisomer, or a pharmaceutically acceptable salt of any one thereof, wherein R5 is selected from -CH=CH2, -CH2-CH3, and -C=CCH3. In some embodiments, the compound is a compound of formula (Ha), (lib), (lie), a stereoisomer, or a pharmaceutically acceptable salt of any one thereof, wherein R6 is selected from hydrogen, and methyl. In some embodiments, the compound is a compound of formula (Ila), (lib), (lie), a stereoisomer, or a pharmaceutically acceptable salt of any one thereof, wherein R9 is selected from -CH=CH2, -CH2-CH3, and -C=CCH3. In some embodiments, the compound is a compound of formula (Ila), (lib), (lie), a stereoisomer, or a pharmaceutically acceptable salt of any one thereof, wherein R10 is selected from hydrogen and methyl. In embodiments, the compound of formula (I) is a compound of formula SMI-1 to SMI-40. In one aspect, the present disclosure relates to an isolated polynucleotide encoding a compound of any of the embodiments disclosed herein. In embodiments, the isolated polynucleotide is or comprises DNA or RNA. In embodiments, the isolated polynucleotide is DNA. In embodiments, the nucleic acid is RNA. In embodiments, the RNA is an mRNA. In embodiments, the mRNA is a modified mRNA (mmRNA). in one aspect, the present disclosure relates to a vector comprising the isolated polynucleotide of any of the embodiments disclosed herein. In one aspect, the present disclosure relates to a pharmaceutical composition comprising a compound of any of the embodiments disclosed herein, or the isolated polynucleotide of any of the embodiments disclosed herein, or the vector of any of the embodiments disclosed herein, or the host cell of any of the embodiments disclosed herein. In one aspect, the present disclosure relates to a pharmaceutical composition comprising a pharmacologically acceptable carrier and: a polypeptide comprising an amino acid sequence that is at least 90%, or at least 95%, or at least 97%, or at least 98% identical to the amino acid sequence of SEQ ID NO 1 or 2; or a peptide comprising an amino acid sequence of any one of SEQ ID NOs: 3-8 or a variant having about 1, 2, 3, 4, 5 or more amino acid mutations with respect to an amino acid sequence selected from SEQ ID NOs: 3 to 8; or a peptide comprising an amino acid sequence of any one of SEQ ID NOs: 9-12 or a variant having about 1, 2, 3, 4, 5 or more amino acid mutations with respect to an amino acid sequence selected from SEQ ID NOs: 9 to 12; or a peptide comprising an amino acid sequence of SEQ ID NO: 15 or a variant having about 1, 2 more amino acid mutations with respect to an amino acid sequence selected from SEQ ID NO: 15. In one aspect, the present disclosure relates to a host cell comprising the isolated polynucleotide of any of the embodiments disclosed herein or the vector of any of the embodiments disclosed herein. In one aspect, the present disclosure relates to a method for treating a cancer, an infectious disease, an inflammatory disease in a subject in need thereof, the method comprising administering to the subject the pharmaceutical composition of any of the embodiments disclosed herein. in embodiments, the cancer is resistant to an anti-checkpoint agent. In embodiments, the anti-checkpoint agent is an antibody. In embodiments, the anti-checkpoint agent an anii-PD-1, anti-PD-L1, anti-PD-L2, and / or anti-CTLAantibody. In embodiments, the antibody is selected from nivolumab (OPDIVO), pembrolizumab (KEYTRUDA), pidilizumab (CT- 011, CURE TECH), MK-3475 (MERCK), BMS 936559. MPDL328OA (ROCHE), Cemipiimab (UBTAYO), Atezolizumab (TECENTRIQ), Avelumab (BAVENCIO), and Durvalumab (imfinzi). In one aspect, the present disclosure relates to a method for treating an anti-checkpoint agent-resistant cancer in a subject in need thereof, the method comprising administering to the subject the pharmaceutical composition of any one of embodiments disclosed herein. In one aspect, the present disclosure relates to a method of determining a cancer treatment for a patient, the method comprising: (a) obtaining a biological sample from a subject; (b) evaluating the biological sample for the expression of Trim?; and (c) selecting the cancer therapy comprising the pharmaceutical composition of any embodiments disclosed herein, if the Trim? is upregulated compared to a compared to a healthy tissue, a prior biological sample obtained from the subject, or another biological sample from patient that is known to be sensitive to an anti-checkpoint agent; and (d) optionally selecting a second cancer therapy comprising an anti-checkpoint agent. In embodiments, the anti-checkpoint agent is selected from an anti-PD-1, anti-PD-L1, anti-PD-L2, and / or anti-CTLA agent. In embodiments, the anticheckpoint agent is selected from an anti-PD-1, anti-PD-L1, anti-PD-L2, and / or anti-CTLA antibody. In one aspect, the present disclosure relates to a method for selecting a patient for a cancer treatment, the method comprising: (a) obtaining a biological sample from a subject; (b) evaluating the biological sample for the expression of Trim?; and (c) selecting the cancer therapy comprising the pharmaceutical composition of any embodiments disclosed herein, if the Trim? is upregulated compared to a compared to a healthy tissue, a prior biological sample obtained from the subject, or another biological sample from patient that is known to be sensitive to an anti-checkpoint agent; and (d) optionally selecting a second cancer therapy comprising an anti-checkpoint agent. In embodiments, the anti-checkpoint agent is selected from an anti-PD-1, anti-PD-L1, anti-PD-L2, and / or anti-CTLA agent. In embodiments, the anticheckpoint agent is selected from an anti-PD-1, anti-PD-L1, anti-PD-L2, and / or anti-CTLA antibody. In one aspect, the present disclosure relates to a method of treating cancer, the method comprising: (a) obtaining a biological sample from a subject; (b) evaluating the biological sample for the expression of Trim?; and (c) administering the pharmaceutical composition of any embodiments disclosed herein, if the Trim? is upregulated compared to a compared to a healthy tissue, a prior biological sample obtained from the subject, or another biological sample from patient that is known to be sensitive to an anti-checkpoint agent; and (d) optionally administering a second cancer therapy comprising an anti-checkpoint agent, in embodiments, the anti-checkpoint agent is selected from an anti-PD-1, anti-PD-L1, anii-PD-L2, and / or anti-CTLA agent. In embodiments, the anti-checkpoint agent is selected from an anti-PD-1, anti-PD-LI, anti-PD-L2, and / or anti-CTLA antibody. Any aspect or embodiment disclosed herein can be combined with any other aspect or embodiment as disclosed herein. BRIEF DESCRIPTION OF THE FIGURES The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee. FIG. 1A to FIG. 1E show the in vitro binding of recombinant human (rh) Trim? to RAC01, MSK1 and stimulator of interferon genes (STING) as measured using a Meso Scale Discovery (MSD) platform-based assays. FIG. 1A and FIG. 1B show the binding of human Trim? to recombinant human RAC01 protein. FIG. 1C and FIG. 1D show the binding of human Trim? to human MSK protein. FIG. 1E show the binding of human Trim? to recombinant human STING protein. FIG. 2 shows the binding of recombinant human (rh) Trim7 to enterovirus 71 2B or enterovirus 71 2BC proteins in vitro as measured using a Meso Scale Discovery (MSD) platform-based assay. Recombinant human RAC01 and MSK1 proteins were used as positive controls and recombinant human CD47 protein was used as a negative control. FIG. 3A and FIG. 3B show that the enterovirus 71 2BC protein inhibits the binding of recombinant human (rh) Trim7 to MSK1 (FIG. 3A) and RAC01 (FIG. 3B) in vitro as measured using a Meso Scale Discovery (MSD) platform-based assay. FIG. 4 shows the crystal structure of Trim7 bound to the CVB_2C (319-329) peptide (SVGTTLEALFQ, SEQ ID NO: 16), which is the C-terminal fragment of the Coxsackievirus B3 (CVB3)_2C protein. Top panel shows a schematic representation of the CVB3 C2 protein, showing the location of the CVB_2C (319-329) peptide. Bottom panel shows crystal structure of CVB_2C protein, showing the CVB_2C (319-329) peptide, and a crystal structure of the Trim7 protein complexed with the CVB_2C (319-329) peptide. FIG. 5A and FIG. 5B show that peptides of SEQ ID NO: 5 (FIG. 5A) and SEQ ID NO: 11 (FIG. 5B) disclosed herein bind to recombinant human Trim7 in vitro, in a C-terminal Gin-dependent manner, as measured using a Meso Scale Discovery (MSD) platform-based assay. FIG. 6A, FIG. 6B, and FIG. 6C show the elucidation of the Trim7 crystal structure that partially informed the Trim7 SMIs of the present disclosure. FIG. 7 provides data confirming TRIM7 interactions with RACO-1, STING, MAVS, and CVB3_2C (WT but not mutant). FIG. 8 is a scheme showing an exemplary workflow for screening and prioritizing candidates. FIG. 9 depicts the screening of the top SMI candidates. SMI Disruption of CVB3 Peptide from TRIM7 was studied using fluorescence polarization (FP). FIG. 10A, FIG. 10B, and FIG. 10C demonstrate that TRIM7 SMIs specifically bind C501 in PrySpry domain using mass spectrometry intact mass and peptide mapping. DETAILED DESCRIPTION Disclosed herein are Trim? inhibitors that are useful, inter alia, for the treatment of disease, such as therapies for cancer, including cancers that are resistant to anti-checkpoint agents, infectious diseases and autoimmunity. Drug resistance, either existing before treatment (intrinsic or primary resistance) or developed after therapy (acquired resistance), is responsible for many relapses of cancer, one of the major causes of death. Therefore, better understanding the mechanisms of drug resistance is required to provide guidance to future cancer treatment. It was reported that anti-PD-1 resistant tumors exhibit a paradoxical dysregulation of some IFNy-induced genes, with Trim7 being a driver gene involved in the paradoxical dysregulation, and anti-PD-1 resistance. See International Application No. PCT / US2021 / 061834, which is incorporated herein by reference in its entirety. Accordingly, disclosed herein are Trim? inhibitors that are useful, inter alia, for the treatment of cancers that are resistant to anti-checkpoint agents. Since Trim? is involved in diverse processes such as tumor growth, innate immunity and pathogenesis of viral infection, the Trim? inhibitors disclosed herein find use in the treatment of cancer, infectious diseases and autoimmunity. Trim7 Tripartite motif (TRIM) proteins are a group of E3 ubiquitin ligases that are involved in different cellular functions. Many TRIM proteins are induced by type I and type II interferons (IFN-I or IFN-II) or pathogen stimulations, in different cell types including human and mouse primary immune cells. Rajsbaum et al., Type I interferon-dependent and -independent expression of tripartite motif proteins in immune cells. Eur J Immunol. 2008;38(3):619-630; Carthagena etal., Human TRIM gene expression in response to interferons. PLoS One 2009;4(3):e4894. The consensus N-terminal region of TRI M proteins contains a RING finger domain followed by one or two B-box domains and a coiled-coil domain (CC). Each TRIM protein has a specific C-terminal domain, which confers substrate specificity via protein-protein interactions. The C-terminal domains include PRY and / or SPRY domains (B30.2). Tripartite Motif Containing 7 (Trim7) is known to have roles in tumor cell proliferation, glycogen metabolism, innate immunity (e.g, via IFN induction), virus pathogenesis. Giraldo etal., Envelope protein ubiquitination drives entry and pathogenesis of Zika virus. Nature 2020. 10.1038 / s41586-020-2457-8; Montori-Grau etal., GNIP1 E3 ubiquitin ligase is a novel player in regulating glycogen metabolism in skeletal muscle. Metabolism. 2018;83:177-187; Lu etal., E3 ubiquitin ligase tripartite motif 7 positively regulates the TLR4-mediated immune response via its E3 ligase domain in macrophages. Mol Immunol. 2019;109:126-133. Without wishing to be bound by theory, it is believed that MSK1 directly phosphorylates Trim7. Trim7 has also been shown to act as an E3 ligase mediating K63-linked polyubiquitination of the AP-1 coactivator RACO-1, leading to RACO-1 protein stabilization. Chakraborty etal., The E3 ubiquitin ligase Trim7 mediates c-Jun / AP-1 activation by Ras signalling. Wat Commun. 2015;6:6782. Trim7 has also been described to negatively regulate responses to DNA viruses by targeting STING for degradation. Yang et al., RNF90 negatively regulates cellular antiviral responses by targeting MITA for degradation. PLoS Pathog. 2020; 16(3):e1008387. Trim? was identified as one of the genes that was identified as dysregulated in model of acquired resistance for an anti-PD-1 antibody. See International Application No. PCT / US2021 / 061834, which is incorporated herein by reference in its entirety. Trim7 Inhibitors Disclosed herein are peptide inhibitors of Trim? inhibitors. In one aspect, the present disclosure relates to a Trim? inhibitor compound of the formula (I): L1-(([Aaa]w)n-[Aaa]x-[Aaa]y-[Aaa]z-Ter)-L2. In embodiments, L1 and / or L2 are independently present or absent; and L1 and / or L2, if present, are each independently selected from a carrier protein, a tag, and a chemical group, the chemical group is optionally selected from acryloyl, amino, alkyl, acyl group, a glycosyl moiety, and a polymer. In embodiments, each [Aaa]w is independently selected from an amino acid. In embodiments, Ter is an amino acid. In embodiments, Ter is Gin or Asn. In embodiments, n = 0-20. In embodiments, [Aaa]x is absent or is an amino acid. In embodiments, [Aaa]y is absent or is an amino acid. In embodiments, [Aaa]z is a hydrophobic or aromatic amino acid; and Ter is Gin or Asn. In embodiments, Ter is Gin. In embodiments, Ter is Asn. In embodiments, [Aaa]zis an aromatic amino acid selected from Tyr, Trp, Phe, and 3-methyl-Phe. In embodiments, the the nitrogen of the aromatic amino acid (e.g. Tyr, Trp, Phe, and 3-methyl-Phe) is substituted with an alkyl group. In embodiments, the nitrogen of the aromatic amino acid is (e.g. Tyr, Trp, Phe, and 3-methyl-Phe) substituted with a methyl group. In embodiments, [Aaa]zis Phe. In embodiments, [Aaa]z is 3-methyl-Phe. In embodiments, [Aaa]z is N-methyl-Phe. In embodiments, [Aaa]z is Trp. In embodiments, [Aaa]zis Tyr. In embodiments, [Aaa]zis a hydrophobic amino acid selected from Leu, Vai, He, Ala, 3-(pyridin-4-yl)-Ala and 3-(pyridin-3-yl)-Ala. In embodiments, [Aaa]zis Leu. In embodiments, [Aaa]zisVal. In embodiments, [Aaa]zis lie. In embodiments, [Aaa]zisAla. In embodiments, [Aaa]zis 3-(pyridin-4-yl)-Ala. In embodiments, [Aaa]zis 3-(pyridin-3-yl)-Ala. In embodiments, [Aaa]zis Met. In embodiments, [Aaa]x and / or [Aaa]y is present and each is independently a natural amino acid. In embodiments, [Aaa]y is present and is a nonpolar amino acid, aromatic amino acid or a polar amino acid. In embodiments, [Aaa]y is a nonpolar amino acid selected from Vai, Gly, Ala, Leu, Met, Trp, Phe, lie, and Pro or an analogue thereof. In embodiments, [Aaa]y is selected from Leu, Trp, and Pro or an analogue thereof. In embodiments, [Aaa]yis Leu. In embodiments, [Aaa]yis Pro or an analogue thereof. In embodiments, [Aaa]y is (R)-p-Pro. In embodiments, (R)-p-Pro comprises ° ? |—I— 5                 . In embodiments, [Aaa]yis (S)-|3-Pro. In embodiments, (S)-|3-Pro comprises 5                 . In embodiments, [Aaa]y is (R)-Pro. In embodiments, [Aaa]y is (S)-Pro. In embodiments, the alpha carbon of the Pro is substituted with an alkyl group. In embodiments, the alpha carbon of the Pro is substituted with a methyl group. In embodiments, [Aaa]y is (S)-a-methyl-Pro. In embodiments, [Aaa]y is (R)-a-methyl-Pro. In embodiments, [Aaa]y is a-methyl-L-proline. In embodiments, [Aaa]y is 3-(4-pyridyl)-L-alanine. In embodiments, [Aaa]yis Gly. In embodiments, the alpha carbon of the Gly is substituted with an alkyl or cyloalkyl group. In embodiments, the alpha carbon of the Gly is substituted with a cyclopropyl group. In embodiments, [Aaa]y is a-cyclopropane-Gly. In embodiments, the beta carbon of the Ala is substituted with an aryl or heteroaryl group. In embodiments, the beta carbon of the Ala is substituted with a pyridine group. In embodiments, [Aaa]y is 3-(pyridin-4-yl)-Ala. In embodiments, [Aaa]y is 3-(pyridin-3-yl)-Ala. In embodiments, [Aaa]yis a polar amino acid selected from Ser, Thr, Gin and Asn. In embodiments, the polar amino acid is a charged amino acid selected from Lys, Arg, His, Glu and Asp. In embodiments, [Aaa]y is an aromatic amino acid selected from Tyr, Trp and Phe. In embodiments, [Aaa]y is Tyr. In embodiments, [Aaa]yis a hydrophobic amino acid selected from Vai, Leu, and lie. In embodiments, [Aaa]yis Leu. In embodiments, [Aaa]x is present and is a nonpolar amino acid, aromatic amino acid or a polar amino acid. In embodiments, [Aaa]xis a nonpolar amino acid selected from Vai, Gly, Ala, Leu, Met, Trp, Phe, lie, and Pro or an analogue thereof. In embodiments, [Aaa]xis Ala. In embodiments, [Aaa]xis an aromatic amino acid selected from Tyr, Trp and Phe. In embodiments, [Aaa]xis Phe. In embodiments, [Aaa]xis a polar amino acid selected from Ser, Thr, Gin and Asn. In embodiments, [Aaa]xis Thr. In embodiments, [Aaa]xis Pro or an analogue thereof. In embodiments, [Aaa]x is (R)-p-Pro. In embodiments, (R)-P-Pro comprises 0 In embodiments, [Aaa]x is (S)-p-Pro. In embodiments, (S)-p-Pro comprises ‘                . In embodiments, [Aaa]x is absent. In embodiments, [Aaa]x is absent and [Aaa]y is selected from Leu and Tyr. In embodiments, [Aaa]x is absent and [Aaa]yis Leu. In embodiments, [Aaa]x is absent and [Aaa]yis Pro or an analogue thereof. In embodiments, [Aaa]xis absent and [Aaa]y is (R)-p-Pro. In embodiments, [Aaa]xis absent and [Aaa]y is (S)-0-Pro. In embodiments, [Aaa]y is absent. In embodiments, [Aaa]y is absent and [Aaa]x is Pro or an analogue thereof. In embodiments, [Aaa]y is absent and [Aaa]x is (R)-P-Pro. In embodiments, [Aaa]y is absent and [Aaa]x is (S)-p-Pro. In embodiments, L1 is present. In embodiments, L1 is present and is acryloyl. In embodiments, L1 is present and is an acyl group. In embodiments, L1 is -CfOlCHs. In embodiments, L1 is -C(O)CH2CH3. In embodiments, L1 is - C(0)CH=CH2. In embodiments, L1 is -C(0)-C=C-CH3. In embodiments, L2 is present. In embodiments, L2 is present and is amino. In embodiments, L2 is -NH2. In embodiments, L2 is -OCH3. In embodiments, L2 is methyl. In embodiments, the Trim7 inhibitor compound comprises at least one, or at least two, or at least three, or at least 4, or at least 5, or at least 6, or at least 7, or at least 8, or at least 9 or at least 10, or at least 15, or more [Aaa]w. In embodiments, each [Aaa]weach is independently a natural amino acid. In embodiments, each [Aaa]wis independently selected from a nonpolar amino acid, aromatic amino acid or a polar amino acid. In embodiments, [Aaa]w is absent (e.g. n = 0). In embodiments, one or more of [Aaa]w, [Aaa]xand [Aaa]yare present and are independently naturally modified amino acids. In embodiments, the naturally modified amino acids or non-standard amino acids are one or more of 4-hydroxyproline and 5-hydroxylysine, and glycosylated amino acids. In embodiments, the compound of formula (I) is selected from L1-Phe-Gln, L1-Leu-Phe-Gln, L1-Leu-Phe-Gln-L2, L1-Leu-3-methyl-Phe-Gln, L1-(R)-|3-Pro-Phe-Gln, and L1-(S)-|3-Pro-Phe-Gln. In embodiments, the compound of formula (I) is selected from L1-Phe-Gln, L1-Leu-Phe-Gln, L1-Leu-Phe-Gln-L2, L1-Leu-3-methyl-Phe-Gln, L1-(R)-|3-Pro-Phe-Gln, and L1-(S)-|3-Pro-Phe-Gln, optionally wherein L1 is an acyl group or acryloyl and optionally wherein L2 is amino. In embodiments, the compound of formula (I) is selected from L1-Phe-Gln, L1-Leu-Phe-Gln, L1-Leu-Phe-Gln-L2, L1-Leu-3-methyl-Phe-Gln, L1-(R)-|3-Pro-Phe-Gln, and L1-(S)-|3-Pro-Phe-Gln, optionally wherein L1 is an acyl group or acryloyl and optionally wherein L2 is amino. In embodiments, L1 is an acyl group. In embodiments, L2 is amino. In embodiments, L1 is -C(O)CH3. In embodiments, L1 is -C(O)CH2CH3. In embodiments, L1 is -C(O)CH=CH2. In embodiments, L1 is -C(O)-C=C-CH3. In embodiments, L2 is -NH2. In embodiments, L2 is -OCH3. In embodiments, L2 is methyl. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof: Formula (II) wherein: R1a, and R1b are at each occurrence independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted 5 heteroarylalkyl; R2 is selected from hydrogen, unsubstituted or substituted alkyl, and unsubstituted or substituted alkylaryl; Y is selected from -0R3a, and -NR3bR3c; R3a, R3b and R3c are at each occurrence independently selected from hydrogen, unsubstituted or substituted 10 alkyl, unsubstituted or substituted alkylaryl, and unsubstituted or substituted aryl; optionally wherein R3b and R3c are joined to form an optionally substituted cycloalkyl; R4a and R4b are at each occurrence independently selected from hydrogen, unsubstituted or substituted alkyl, and unsubstituted or substituted alkylaryl, optionally wherein R4a and R4b are joined to form an optionally substituted cycloalkyl; R5 is selected from unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted aryl, and unsubstituted or substituted alkylaryl; R6 is selected from hydrogen, unsubstituted or substituted alkyl, and unsubstituted or substituted alkylaryl; R7 is selected from unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted aryl, and unsubstituted or substituted alkylaryl; R8a and R8b are at each occurrence independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl, optionally wherein R8a and R8b are joined to form an optionally substituted cycloalkyl; R9 is selected from unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted aryl, and unsubstituted or substituted alkylaryl; and R10 is selected from hydrogen, unsubstituted or substituted alkyl, and unsubstituted or substituted alkylaryl. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein Y is selected from -OH, OCH3, NH2, NHMe, and NMe2. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R1a is hydrogen and R1b is selected from: wherein R11 is selected from hydrogen, unsubstituted or substituted alkyl, and unsubstituted or substituted alkylaryl. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R11 is methyl. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R1a and R1b are at each occurrence independently selected from: In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R4a and R4b are at each occurrence independently selected from hydrogen, methyl, isopropyl, and isobutyl. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R2 is selected from hydrogen, methyl, isopropyl, and isobutyl. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R2 is selected from hydrogen and methyl. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R5 is selected from -CH=CH2, -CH2-CH3, and -C^CCHs. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R6 is selected from hydrogen, and methyl. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R7 is selected from -CH3, -CH=CH2, -CH2-CH3, and -0=001¼ 5 In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R8a is hydrogen and R8b is selected from hydrogen, methyl, isopropyl, and isobutyl. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R8a and R8b are joined to form an optionally substituted cycloalkyl; optionally R8a and R8b are joined to form cyclopropyl. 10 In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R9 is selected from -CH=CH2, -CH2-CH3, and -C=CCH3. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R10 is selected from hydrogen and methyl. In embodiments, the compound is a compound of formula (Ila), a stereoisomer, or a pharmaceutically acceptable salt 15 thereof: Formula (Ila). In embodiments, the compound is a compound of formula (lib), a stereoisomer, or a pharmaceutically acceptable salt thereof: Formula (lib). In embodiments, the compound is a compound of formula (lie), a stereoisomer, or a pharmaceutically acceptable salt thereof: Formula (lie). In embodiments, the compound is a compound of formula (Illa), a stereoisomer, or a pharmaceutically acceptable salt thereof: 10 Formula (Illa). In embodiments, the compound is a compound of formula (lllb), a stereoisomer, or a pharmaceutically acceptable salt thereof: Formula (lllb). In some embodiments, the compound is a compound of formula (Ila), (lib), (lie), (Illa), (lllb), a stereoisomer, or a pharmaceutically acceptable salt of any one thereof, wherein R1b is selected from: In some embodiments, the compound is a compound of formula (Ila), (lib), (lie), (Illa), (lllb), a stereoisomer, or a pharmaceutically acceptable salt of any one thereof, wherein R2 is selected from hydrogen and methyl. In some embodiments, the compound is a compound of formula (Ila), (lib), (He), (Illa), (lllb), a stereoisomer, or a pharmaceutically acceptable salt of any one thereof, wherein X is selected from -CH=CH2, In some embodiments, the compound is a compound of formula (Ila), (lib), (He), (Illa), (lllb), a stereoisomer, or a pharmaceutically acceptable salt of any one thereof, wherein R4a and R4b are at each occurrence independently selected from hydrogen and methyl. In some embodiments, the compound is a compound of formula (Illa), (lllb), a stereoisomer, or a pharmaceutically acceptable salt of any one thereof, wherein R8b is isobutyl. In some embodiments, the compound is a compound of formula (Ila), (lib), (He), (Illa), (lllb), a stereoisomer, or a pharmaceutically acceptable salt of any one thereof, wherein R7 is selected from -CH3, -CH=CH2, -CH2-CH3, and -C=CCH3. In some embodiments, the compound is a compound of formula (Ha), (lib), (lie), a stereoisomer, or a pharmaceutically acceptable salt of any one thereof, wherein R5 is selected from -CH=CH2, -CH2-CH3, and -C=CCH3. In some embodiments, the compound is a compound of formula (Ha), (lib), (lie), a stereoisomer, or a pharmaceutically acceptable salt of any one thereof, wherein R6 is selected from hydrogen, and methyl. In some embodiments, the compound is a compound of formula (Ila), (lib), (lie), a stereoisomer, or a pharmaceutically acceptable salt of any one thereof, wherein R9 is selected from -CH=CH2, -CH2-CH3, and -C=CCH3. In some embodiments, the compound is a compound of formula (Ila), (lib), (lie), a stereoisomer, or a pharmaceutically acceptable salt of any one thereof, wherein R10 is selected from hydrogen, and methyl. 5 In embodiments, the compound of formula (I) is a compound of formula SMI-1 to SMI-40: Formula No. Structure SMI-1 ,0 0  f H  ?  f A A N  .X A OH N V   N V b H         ? H \ ..... / CH2=CHC(O)-Leu-Phe-GIn SMI-2 HSN .^.,0 0            0 f"' H 0 CH2=CHC(O)-Leu-Phe-Gln-NH2 SMI-3 0         0 ;;       I       H       ss A A N  A < N V    CH n 0 ...A CH2=CHC(O)-Phe-GIn SMI-4 H.A ,0 . ■:        f n       s>       t A A N a -A OH A N" Y" 'A N’ V ;       0 a      0 F"S CH3-CH2C(O)-Leu-Phe-GIn SMI-5 , , 0 CH3C(O)Leu-Phe-GIn 0        '7, o Z" । n n i c 5 7 \ / '' 7 x X”--O / / SMI-6 0   | H XX / .. 7 7     \ ...... x    b .X CH3C(O)-Leu-Phe-Gln-NH2 SMI-7 7 3 l" "N" x" H ]....... XX / .... -¾ * *'               *                                              CX2 o-b   •— b b X CH3-CH2C(O)-Leu-Phe-GIn SMI-8 0 ( 'Sr' H2N .^0 "L   0    •"" H       si        :. ■ Nx       ..- OH ?r v n □  \     0 CH2=CHC(O)-Leu-Phe-GIn SMI-9 q    x 7—, q         .......... x        jgx v 'a / ¾. ; xx ......<    —o \ / XX CH3-CH2C(O)- Leu-Phe-Gln-NH2 SMI-10 0 " ’ N " H ' H x - N 0 ......... WAo ......Z x......f o b CH3-CH2C(O)-Leu-3-methyl-Phe-GIn 0 f H F ,N 6 HM,O '° f CH2=CHC(O)-Leu-3-methyl-Phe-GIn SMI-11 'A ' H . .. K 6 0 f V ? CH2=CHC(O)-(S)-p-Pro-Phe-Gln SMI-12 ox A I A'N' H 6 , / cAnh^ 0 f H if CH2=CHC(O)-(R)-p-Pro-Phe-Gln SMI-13 °\ N i ''V'N' H 4. ,NX           , >f      OH 6 ,J 0^-' ' NH? A CH3-CH2C(O)-(S)-p-Pro-Phe-Gln SMI-14 0 -N I H ■L A |f Y OH 6 F \ \ .A 0 Nh? SMI-15 o, z-y ' j § j CH3-CH2C(O)-(R)-p-Pro-Phe-Gln SMI-16 L A A M N j[          OH CH2=CHC(O)-(S)-Pro-Phe-(N5-methyl)-Gln SMI-17 r    x O    2...... / ~\       o ('   ?IZ y     \_$ Q, "Y~~\ J,zj CH2=CHC(O)-(S)-a-methyl-Pro-Phe-(N5-methyl)-Gln SMI-18 u 0          0 ° 0 O^NHj CH2=CHC(O)-Leu-3-(pyridin-4-yl)-Ala-Gln SMI-19 T    X O     22— .--- / V.., / f pxxz z ''•A o r~y. CH2=CHC(O)- (S)-Pro-(N-methyl)-Phe-(N5- methyl)-Gln SMI-20 CH2=CHC(O)- (S)-Pro-(N-methyl)-Phe-Gln v / A z O x z SMI-21 0 S' ^AA A A ^A X     X __ kH O1^ X;z"" /      A"’Q CH2=CHC(O)-Leu-Phe-(N5-methyl)-Gln SMI-22 h ? r d kA aas j :: 6 k ) Ah Ah; CH3-CH2C(O)-Leu-3-(pyridin-4-yl)-Ala-Gln SMI-23 A? ? OA T     X O A / ~C ry / ° CH3-CH2C(O)-(S)-Pro-3-(pyridin-3-yl)-Ala-Gln SMI-24 \     u 0 f V X X 1 I u I ,0 H x >k r r o x oJ 0 Ah CH3-CeC-C(O)-Leu-Phe-GIn SMI-25 T     T4 o    z / ^xz zx 0. A V-x > , / / CH3-CeC-C(O)-(S)-Pro-3-(pyridin-3-yl)-Ala-Gln SMI-26 A 0      0 k A A kA XOr M OH \J H a < O^NH CH3-CeC-C(O)-(S)-Pro-Phe-(N5-methyl)-Gln SMI-27 0 fu 0 kuiAAV u H K O^NH CH2=CHC(O)-(S)-a-methyl-Pro-Phe-(N5-methyl)-Gln-OCH3 SMI-28 ft „                |      | ft zO 0 r 2; 0 AA vJ i 0 k O^'NH, CH2=CHC(O)-(S)-Pro-(N-methyl)-Phe-Gln-och3 SMI-29 LjlX jC$jl V x nr ? oh Z....—x CH2=CHC(O)- a-cyclopropane-Gly-Phe-GIn SMI-30 ° p ° L CH2=CHC(O)-Leu-Phe-(N6,N5-dimethyl)-Gln SMI-31 QAIH2 h ; h 0 CH2=CHC(O)-(S)-Pro-Phe-Gln-och3 SMI-32 CK JMH, A t ' ALA At A CH2=CHC(O)-Leu-Phe-GIn-och3 SMI-33 I U 0             0 0          0 O^XNH;. CH3-CH2C(O)-a-cyclopropane-Gly-Phe-GIn SMI-34 A a / o f    0 ia •A jk JL A' N A< A OH H 61 OAIH^. CH2=CHC(O)-(S)-Pro-Phe-Gln SMI-35 JO / Mr" Mi^a / SSoh O H 0 1 CH2=CHC(O)-(S)-a-methyl-Pro-Phe-GIn SMI-36 a JO   X / A ? A t \M H o O'^NH2 CH2=CHC(O)-(R)-Pro-Phe-Gln SMI-37 A JO o f o o jIAA O H A t O'^NH, CH3-CH2C(O)-(S)-a-methyl-Pro-Phe-GIn SMI-38 Qs z ZT f 1 o / r x CH3-CH2C(O)-(S)-Pro-Phe-Gln SMI-39 ,0   O ''"I A .OJl / >rrr Sr ><'oh v-J H d k 1 0- nh2 CH3-CH2C(O)-(R)-Pro-Phe-Gln CH3-CeC-C(O)-(S)-p-Pro-Phe-Gln In embodiments, L1 and / or L2 is or comprises a carrier protein selected from Fc domain, albumin, transferrin, or elastinlike protein, Keyhole Limpet Hemocyanin (KLH), ovalbulin, or a variant thereof. In embodiments, the carrier protein comprises a Fc domain selected from an IgG Fc domain, an IgA Fc domain, an IgM Fc domain, an IgE Fc domain, and an IgD Fc domain. In embodiments, the carrier protein comprises an IgG Fc domain wherein the IgG Fc domain is selected from an IgG 1 Fc domain, an lgG2 Fc domain, an lgG3 Fc domain, and an lgG4 Fc domain. In embodiments, the carrier protein comprises an IgA domain wherein the IgA domain is selected from an lgA1 Fc domain and an lgA2 Fc domain. In embodiments, the carrier protein is linked at the N-terminus of ([Aaa]w)n-[Aaa]x-[Aaa]y-[Aaa]z-Ter). In embodiments, the carrier protein is linked at the C-terminus of ([Aaa]w)n-[Aaa]x-[Aaa]y-[Aaa]z-Ter). In embodiments, the carrier protein is linked to ([Aaa]w)n-[Aaa]x-[Aaa]y-[Aaa]z-Ter) via a peptide linker. In embodiments, the peptide linker is rigid or flexible. In embodiments, L1 and / or L2 comprises or further comprises a tag. In embodiments, the tag is selected from hexahistidine tag, FLAG tag, Strep II tag, streptavidin-binding peptide (SBP) tag, calmodulin-binding peptide (CBP), glutathione S-transferase (GST), maltose-binding protein (MBP), S-tag, HA tag, and c-Myc tag. In embodiments, L1 and / or L2 comprises or further comprises a glycosyl moiety. In embodiments, the glycosyl moiety is an N-linked glycosyl moiety. In embodiments, the glycosyl moiety is an O-linked glycosyl moiety. In embodiments, the Trim / inhibitor compound comprises one or more N-linked glycosylation consensus sites and / or O-linked glycosylation consensus sites. In embodiments, the one or more N-linked glycosylation consensus sites and / or 0-linked glycosylation consensus sites are present in ([Aaa]w)n-[Aaa]x-[Aaa]y-[Aaa]z-Ter), the carrier protein, or the tag. In embodiments, the N-linked glycosylation consensus site comprises asparagine (Asn or N)-X-serine (Ser or S) / threonine (Thr or T), wherein X is any amino acid other than proline (Pro or P). In embodiments, the O-linked glycosylation consensus site comprises serine (Ser or S) or threonine (Thr or T). In embodiments, L1 is present and is an acryloyl group. As used herein, "acryloyl” refers to -C(0)-CH=CH2. In embodiments, L1 is present and is an acyl group. In embodiments, the acyl group is CH3-CH2-C(O)-, CH3-C(0)-, or CH3-C=C-C(O)-. In embodiments, L2 is present and is an amino group. As used herein, "amino” refers to -N(R3)2, wherein each R3 is independently at each occurrence a group selected from hydrogen and alkyl. In embodiments, the amino group is -NH2. In embodiments, the amino group replaces the -OH group in the carbonyl of Ter. In a non-limiting example, if Ter H2Nxj;>0 H2N^O An>vNh2 Xn^nh2 H a H II is glutamine (Gin) and L2 is an amino group, the structure of Ter is u , u , or h2n^o Zn\nh^ H II 0     . In embodiments, L2 is present and is -OCH3. In embodiments, the -OCH3 group replaces the -OH group in the carbonyl of Ter. In embodiments, the Trim7 inhibitor compound is biosynthesized as a single polypeptide chain. In embodiments, the Trim? inhibitor compound is biosynthesized from a single open reading frame. In embodiments, the Trim7 inhibitor compound is prepared using an expression system. In embodiments, the expression system is selected from bacterial, yeast, invertebrate (e.g., an insect cell), vertebrate (e.g., a mammalian cell), and plant expression system. In embodiments, one or more of [Aaa]w, [Aaa]x and [Aaa]y are present and are independently selected from non-natural amino acids (e.g., D-amino acids (Daa), and those comprising N-methylation (Nm), Go-methylation (Cm), amino isobutyric acids (Aib), ^(C^NH) reduced amide bonds (Rd), and peptoids (Pp)). In embodiments, L1 and / or L2 comprises or further comprises an alkyl or acyl group that is conjugated to the Trim7 inhibitor compound. In embodiments, L comprises an acyl group. In embodiments, the acyl group is CH3-CH2-C(O)-, CH3-C(O)-, or CH3-C=C-C(0)-. In embodiments, the acyl group is an acetyl group. In embodiments, L1 and / or L2 comprises or further comprises a polymer. In embodiments, the polymer is selected from poly(alkylene oxide) (e.g., polyethylene glycol (PEG)), poly (N-vinylpyrrolidone), poly(vinyl alcohol), poly (glycerol), poly(zwitterions), poly(carbonates), polyoxazoline, poly(acryloylmorpholine), poly(oxazolines), poly(sacharrides), and a combination thereof. In embodiments, the polymer is a polyethylene glycol (PEG). In embodiments, one or more amino acids present in the present in ([Aaa]w)n-[Aaa]x-[Aaa]y-[Aaa]z-Ter), the carrier protein, or the tag are PEGylated. In embodiments, one or more PEGylated amino acids comprises Lys and PEGylation is conducted via amine conjugation. In embodiments, one or more PEGylated amino acids comprises Gin and PEGylation is conducted via transglutaminase (TGase) mediated enzymatic conjugation. In embodiments, one or more PEGylated amino acids comprises Cys and PEGylation is conducted via thiol conjugation. In embodiments, the Trim? inhibitor compound comprises the enterovirus 71 (EV71) protein 2BC, which has the following sequence: GVSDYIKGLGRAFGTGFTDAVSREVEALKNHLIGSEGAVEKILKNLVKLISALVIVIRSDYDMVTLTATLALIGCHGSPW AWIKSKTASILGIPMAQKQSASWLKKFNDMANAAKGLEWIFNKISKFIDWLKEKIIPAAKEKVEFLNNLKQLPLLENQVS NLEQSAASQEDLEAMFGNVIYLAHFCRKFQPLYATEAKRVYALEKRMNNYMQFKSKHRIEPVCLIIRGSPGTGKSLAT GIIARAIADKYRSSVYSLPPDPDHFDGYKQQWAVMDDLCQNPDGKDMSLFCQMVSTVDFVPPMASLEEKGVSFTSK FVIASTNASNIIVPTVSDSDAIRRRFYMDCDIEVTDSYKTDLGRLDAGRAAKLCTENNTANFKRCSPLVCGKAIQLRDR KSKVRYSVDTWSELIREYNNRSAIGNTIEALFQ (SEQ ID NO: 1) In embodiments, the present Trim? inhibitor compound comprises EV71 2BC protein or a variant thereof, which has the amino acid sequence of SEQ ID NO: 1. In embodiments, the present Trim? inhibitor compound may comprise EV71 2BC protein as described herein, or a variant or functional fragment thereof. For instance, the Trim7 inhibitor compound may comprise a sequence of EV71 2BC protein as provided above, or a variant or functional fragment thereof having at least about 60%, or at least about 61%, or at least about 62%, or at least about 63%, or at least about 64%, or at least about 65%, or at least about 66%, or at least about 67%, or at least about 68%, or at least about 69%, or at least about 70%, or at least about 71%, or at least about 72%, or at least about 73%, or at least about 74%, or at least about 75%, or at least about 76%, or at least about 77%, or at least about 78%, or at least about 79%, or at least about 80%, or at least about 81%, or at least about 82%, or at least about 83%, or at least about 84%, or at least about 85%, or at least about 86%, or at least about 87%, or at least about 88%, or at least about 89%, or at least about 90%, or at least about 91 %, or at least about 92%, or at least about 93%, or at least about 94%, or at least about 95%, or at least about 96%, or at least about 97%, or at least about 98%, or at least about 99%) sequence identity with the amino acid sequence of SEQ ID NO:1 as described herein. In embodiments, the EV71 2BC protein as provided above, or a variant or functional fragment thereof (e.g., SEQ ID NON or a polypeptide comprising an amino acid sequence that is at least 90%, or at least 95%, or at least 97%, or at least 98% identical to the amino acid sequence of SEQ ID NO 1 binds Trim / protein and inhibits it activity. In embodiments, the Trim / inhibitor compound comprises the enterovirus 71 (EV71) protein 2C, which has the following sequence: GVSDYIKGLGDAFGMGFTDAVSREVEALKNHLIGSEGAVEKILKNLVKLISALVIVIRSDYDMVTLTATLALIGCHGSPW AWVKSKTASILGIPMAQKQ (SEQ ID NO: 2) In embodiments, the present Trim / inhibitor compound comprises EV71 2C protein or a variant thereof, which has the amino acid sequence of SEQ ID NO: 1. In embodiments, the present Trim / inhibitor compound may comprise EV71 20 protein as described herein, or a variant or functional fragment thereof. For instance, the Trim / inhibitor compound may comprise a sequence of EV / 1 20 protein as provided above, or a variant or functional fragment thereof having at least about 60%, or at least about 61 %, or at least about 62%, or at least about 63%, or at least about 64%, or at least about 65%, or at least about 66%, or at least about 67%, or at least about 68%, or at least about 69%, or at least about 70%, or at least about 71%, or at least about 72%, or at least about 73%, or at least about 74%, or at least about 75%, or at least about 76%, or at least about 77%, or at least about 78%, or at least about 79%, or at least about 80%, or at least about 81%, or at least about 82%, or at least about 83%, or at least about 84%, or at least about 85%, or at least about 86%, or at least about 87%, or at least about 88%, or at least about 89%, or at least about 90%, or at least about 91%, or at least about 92%, or at least about 93%, or at least about 94%, or at least about 95%, or at least about 96%, or at least about 97%, or at least about 98%, or at least about 99%) sequence identity with the amino acid sequence of SEQ ID NO:1 as described herein. In embodiments, the EV71 2C protein as provided above, or a variant or functional fragment thereof (e.g., SEQ ID NO: 2 or a polypeptide comprising an amino acid sequence that is at least 90%, or at least 95%, or at least 97%, or at least 98% identical to the amino acid sequence of SEQ ID NO 2 binds Trim7 protein and inhibits it activity. EV71 2BC protein as provided above, EV71 20 protein as provided above, or a variant or functional fragment thereof derivatives can be constructed from available structural data, including that described by Guan et al., Crystal structure of 2C helicase from enterovirus 71, Sci Adv. 2017 Apr 28;3(4): e1602573; Wang et al., The Structure, Function, and Mechanisms of Action of Enterovirus Non-structural Protein 2C, Front Microbiol 2020; 11:615965; and Liang et al., Structural insights into the viral proteins binding by TRIM7 reveal a general C-terminal glutamine recognition mechanism, bioRxiv 2022.03.24.485560. Additional exemplary Trim7 inhibitor compounds are provided below in Table 1: Table 1: Exemplary nonlimiting Trim7 inhibitor compounds of the present disclosure: SEQ ID NO Name Sequence 3 CVB3_2C(322-329) TTLEALFQ 4 His-OVB3_2C(322-329) HHHHHHTTLEALFQ 5 HA-OVB3_2C(322-329) YPYDVPDYATTLEALFQ 6 Flag-CVB3_2C(322-329) DYKDDDDKTTLEALFQ 7 His-CVB3_2C(Q329A) HHHHHHTTLEALFA 8 HA-CVB3_2C(Q329A) YPYDVPDYATTLEALFA 9 GN1_2O(322-329) RKLDTYLQ 10 His-GN1_2C(322-329) HHHHHHRKLDTYLQ 11 HA-GN1_2C(322-329) YPYDVPDYARKLDTYLQ 12 Flag-GN1_2C(322-329) DYKDDDDKRKLDTYLQ 13 His-GN1_2C(Q329A) HHHHHHRKLDTYLA 14 HA-GN1_2C(Q329A) YPYDVPDYARKLDTYLA 15 CVB3_2C (Ac-326-329) Ac-ALFQ *predicted inactive peptides are lacking amino acid gluatmine Q, which is substituted with an alanine A (underlined text), at C terminus. In embodiments, the Trim? inhibitor compound comprises an amino acid sequence of any one of SEQ ID NOs: 1-15. In embodiments, the Trim? inhibitor compound comprises an amino acid sequence of any one of SEQ ID NOs: 3-15. In embodiments, the Trim? inhibitor compound comprises an amino acid sequence of any one of SEQ ID NOs: 3-8. In embodiments, the Trim? inhibitor compound comprises an amino acid sequence of any one of SEQ ID NOs: 9-12. In embodiments, the Trim? inhibitor compound comprises an amino acid sequence of any one of SEQ ID NO: 15. In embodiments, the Trim? inhibitor compound comprises an amino acid sequence of any one of SEQ ID NOs: 1-15 or a variant having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid mutations with respect to an amino acid sequence selected from SEQ ID NOs: 1 to 15. In embodiments, the Trim? inhibitor compound comprises an amino acid sequence of any one of SEQ ID NOs: 3-15, or a variant having about 1, 2, 3, 4, 5 or more amino acid mutations with respect to an amino acid sequence selected from SEQ ID NOs: 3 to 15. In embodiments, the Trim? inhibitor compound comprises an amino acid sequence of any one of SEQ ID NOs: 3-8 or a variant having about 1, 2, 3, 4, 5 or more amino acid mutations with respect to an amino acid sequence selected from SEQ ID NOs: 3 to 8. In embodiments, the Trim? inhibitor compound comprises an amino acid sequence of any one of SEQ ID NOs: 9-12 or a variant having about 1, 2, 3, 4, 5 or more amino acid mutations with respect to an amino acid sequence selected from SEQ ID NOs: 9 to 12. In embodiments, the Trim? inhibitor compound comprises an amino acid sequence of any one of SEQ ID NO: 15 or a variant having about 1, 2, or more amino acid mutations with respect to an amino acid sequence selected from SEQ ID NO: 15. In embodiments, the Trim? inhibitor compound comprises an amino acid sequence identical to that of SEQ ID NO: 115, or a variant having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid mutations with respect to an amino acid sequence selected from SEQ ID NOs: 1 to 15. In embodiments, the amino acid mutations are amino acid substitutions, and may include conservative and / or nonconservative substitutions. “Conservative substitutions” may be made, for instance, on the basis of similarity in polarity, charge, size, solubility, hydrophobicity, hydrophilicity, and / or the amphipathic nature of the amino acid residues involved. The 20 naturally occurring amino acids can be grouped into the following six standard amino acid groups: (1) hydrophobic: Met, Ala, Vai, Leu, lie; (2) neutral hydrophilic: Cys, Ser, Thr; Asn, Gin; (3) acidic: Asp, Glu; (4) basic: His, Lys, Arg; (5) residues that influence chain orientation: Gly, Pro; and (6) aromatic: Trp, Tyr, Phe. As used herein, “conservative substitutions” are defined as exchanges of an amino acid by another amino acid listed within the same group of the six standard amino acid groups shown above. For example, the exchange of Asp by Glu retains one negative charge in the so modified polypeptide. In addition, glycine and proline may be substituted for one another based on their ability to disrupt o-helices. As used herein, “non-conservative substitutions" are defined as exchanges of an amino acid by another amino acid listed in a different group of the six standard amino acid groups (1) to (6) shown above. In embodiments, the substitutions may also include non-classical amino acids (e.g., selenocysteine, pyrrolysine, N-formylmethionine p-alanine, GABA and 5-Aminolevulinic acid, 4-aminobenzoic acid (PABA), D-isomers of the common amino acids, 2,4-diaminobutyric acid, a-amino isobutyric acid, 4-aminobutyric acid, Abu, 2-amino butyric acid, y-Abu, e-Ahx, 6-amino hexanoic acid, Aib, 2-amino isobutyric acid, 3-amino propionic acid, ornithine, norleucine, norvaline, hydroxy proline, sarcosme, citrulline, homocitrulline, cysteic acid, t-butylglycine, t-butylalanine, phenylglycine, cyclohexylalanine, p-alanine, fluoro-amino acids, designer amino acids such as |3 methyl amino acids, C a-methyl amino acids, N a-methyl amino acids, and amino acid analogs in general). Mutations may also be made to the nucleotide sequences of the Trim? inhibitor compounds by reference to the genetic code, including taking into account codon degeneracy. In embodiments, the Trim / inhibitor compound comprises a linker. In embodiments, the linker comprising at least one cysteine residue capable of forming a disulfide bond. As described elsewhere herein, such at least one cysteine residue capable of forming a disulfide bond is, without wishing to be bound by theory, responsible for maintain a proper multimeric state of the Trim / inhibitor compound and allowing for efficient production. In embodiments, the linker may be derived from naturally-occurring multi-domain proteins or are empirical linkers as described, for example, in Chichili et al., (2013), Protein Sci. 22(2):153-167, Chen et al., (2013), Adv Drug Deliv Rev. 65(10):1357-1369, the entire contents of which are hereby incorporated by reference. In embodiments, the linker may be designed using linker designing databases and computer programs such as those described in Chen et al., (2013), Adv Drug Deliv Rev. 65(10):1357-1369 and Crasto et. al., (2000), Protein Eng. 13(5):309-312, the entire contents of which are hereby incorporated by reference. Pharmaceutical compositions Aspects of the present disclosure include a pharmaceutical composition comprising the Trim? inhibitors any of the herein disclosed aspects or embodiments. In one aspect, the present disclosure relates to a pharmaceutical composition comprising a Trim? inhibitor compound of any of the embodiments disclosed herein, or the isolated polynucleotide of any of the embodiments disclosed herein, or the vector of any of the embodiments disclosed herein, or the host cell of any of the embodiments disclosed herein. Accordingly, in one aspect, the present disclosure provides a pharmaceutical composition comprising a Trim? inhibitor compound of the formula (I): L1-(([Aaa]w)n-[Aaa]x-[Aaa]y-[Aaa]z-Ter)-L2. In embodiments, L1 and / or L2 are independently present or absent; and L1 and / or L2, if present, are each independently selected from a carrier protein, a tag, and a chemical group, the chemical group is optionally selected from acryloyl, amino, alkyl, acyl group, a glycosyl moiety, and a polymer. In embodiments, each [Aaa]w is independently selected from an amino acid. In embodiments, Ter is an amino acid. In embodiments, Ter is Gin or Asn. In embodiments, n = 0-20. In embodiments, [Aaa]x is absent or is an amino acid. In embodiments, [Aaa]y is absent or is an amino acid. In embodiments, [Aaa]z is an hydrophobic or aromatic amino acid; and Ter is Gin or Asn. In embodiments, Ter is Gin. In embodiments, Ter is Asn. In embodiments, [Aaa]zis an aromatic amino acid selected from Tyr, Trp, Phe, and 3-methyl-Phe. In embodiments, the nitrogen of the aromatic amino acid is (e.g. Tyr, Trp, Phe, and 3-methyl-Phe) substituted with an alkyl group. In embodiments, the nitrogen of the aromatic amino acid is (e.g. Tyr, Trp, Phe, and 3-methyl-Phe) substituted with a methyl group. In embodiments, [Aaa]zis Phe. In embodiments, [Aaa]z is 3-methyl-Phe. In embodiments, [Aaa]z is N-methyl-Phe. In embodiments, [Aaa]z is Trp. In embodiments, [Aaa]zis Tyr. In embodiments, [Aaa]zis a hydrophobic amino acid selected from Leu, Vai, He, Ala, 3-(pyridin-4-yl)-Ala and 3-(pyridin-3-yl)-Ala. In embodiments, [Aaa]zis Leu. In embodiments, [Aaa]zisVal. In embodiments, [Aaa]zis lie. In embodiments, [Aaa]zisAla. In embodiments, [Aaa]zis 3-(pyridin-4-yl)-Ala. In embodiments, [Aaa]zis 3-(pyridin-3-yl)-Ala. In embodiments, [Aaa]zis Met. In embodiments, [Aaa]x and / or [Aaa]y is present and each isindependently a natural amino acid. In embodiments, [Aaa]y is present and is a nonpolar amino acid, aromatic amino acid or a polar amino acid. In embodiments, [Aaa]y is a nonpolar amino acid selected from Vai, Gly, Ala, Leu, Met, Trp, Phe, lie, and Pro or an analogue thereof. In embodiments, [Aaa]y is selected from Leu, Trp, and Pro or an analogue thereof. In embodiments, [Aaa]y is Leu. In embodiments, [Aaa]yis Pro or an analogue thereof. In embodiments, [Aaa]yis (R)-p-Pro. In embodiments, [Aaa]yis (S)-P-Pro. In embodiments, [Aaa]y is (R)-Pro. In embodiments, [Aaa]yis (S)-Pro. In embodiments, the alpha carbon of the Pro is substituted with an alkyl group. In embodiments, the alpha carbon of the Pro is substituted with a methyl group. In embodiments, [Aaa]yis (S)-a-methyl-Pro. In embodiments, [Aaa]y is (R)-a-methyl-Pro. In embodiments, [Aaa]y is a-methyl-L-proline. In embodiments, [Aaa]y is 3-(4-pyridyl)-L-alanine. In embodiments, [Aaa]yis Gly. In embodiments, the alpha carbon of the Gly is substituted with an alkyl or cyloalkyl group. In embodiments, the alpha carbon of the Gly is substituted with a cyclopropyl group. In embodiments, [Aaa]yis a-cyclopropane-Gly. In embodiments, the beta carbon of the Ala is substituted with an aryl or heteroaryl group. In embodiments, the beta carbon of the Ala is substituted with a pyridine group. In embodiments, [Aaa]y is 3-(pyridin-4-yl)-Ala. In embodiments, [Aaa]y is 3-(pyridin-3-yl)-Ala. In embodiments, [Aaa]yis a polar amino acid selected from Ser, Thr, Gin and Asn. In embodiments, the polar amino acid is a charged amino acid selected from Lys, Arg, His, Glu and Asp. In embodiments, [Aaa]y is an aromatic amino acid selected from Tyr, Trp and Phe. In embodiments, [Aaa]yis Tyr. In embodiments, [Aaa]yis a hydrophobic amino acid selected from Vai, Leu, and lie. In embodiments, [Aaa]yis Leu. In embodiments, [Aaa]x is present and is a nonpolar amino acid, aromatic amino acid or a polar amino acid. In embodiments, [Aaa]xis a nonpolar amino acid selected from Vai, Gly, Ala, Leu, Met, Trp, Phe, lie, and Pro or an analogue thereof. In embodiments, [Aaa]x is Ala. In embodiments, [Aaa]x is an aromatic amino acid selected from Tyr, Trp and Phe. In embodiments, [Aaa]xis Phe. In embodiments, [Aaa]xis a polar amino acid selected from Ser, Thr, Gin and Asn. In embodiments, [Aaa]xis Thr. In embodiments, [Aaa]xis Pro or an analogue thereof. In embodiments, [Aaa]x is (R)-|3-Pro. In embodiments, [Aaa]xis (S)-p-Pro. In embodiments, [Aaa]x is absent. In embodiments, [Aaa]x is absent and [Aaa]y is selected from Leu and Tyr. In embodiments, [Aaa]x is absent and [Aaa]yis Leu. In embodiments, [Aaa]x is absent and [Aaa]yis Pro or an analogue thereof. In embodiments, [Aaa]x is absent and [Aaa]yis (R)-|3-Pro. In embodiments, [Aaa]xis absent and [Aaa]yis (S)-|3-Pro. In embodiments, [Aaa]y is absent. In embodiments, [Aaa]y is absent and [Aaa]x is Pro or an analogue thereof. In embodiments, [Aaa]y is absent and [Aaa]x is (R)-p-Pro. In embodiments, [Aaa]y is absent and [Aaa]x is (S)-p-Pro. In embodiments, L1 is present. In embodiments, L1 is present and is acryloyl. In embodiments, L1 is present and is an acyl group. In embodiments, L1 is -C(0)CH3. In embodiments, L1 is -C(O)CH2CH3. In embodiments, L1 is -C(0)CH=CH2. In embodiments, L1 is -C(0)-C=C-CH3. In embodiments, L2 is present. In embodiments, L2 is present and is amino. In embodiments, L2 is -NH2. In embodiments, L2 is -OCH3. In embodiments, L2 is methyl. In embodiments, the Trim7 inhibitor compound comprises at least one, or at least two, or at least three, or at least 4, or at least 5, or at least 6, or at least 7, or at least 8, or at least 9 or at least 10, or at least 15, or more [Aaa]w. In embodiments, each [Aaa]weach is independently a natural amino acid. In embodiments, each [Aaa]w is independently selected from a nonpolar amino acid, aromatic amino acid or a polar amino acid. In embodiments, [Aaa]wis absent (e.g., n = 0). In embodiments, one or more of [Aaa]w, [Aaa]xand [Aaa]yare present and are independently naturally modified amino acids. In embodiments, the naturally modified amino acids or non-standard amino acids are one or more of 4-hydroxyproline and 5-hydroxylysine, and glycosylated amino acids. In embodiments, the compound of formula (I) is selected from L1-Phe-Gln, L1-Leu-Phe-Gln, L1-Leu-Phe-Gln-L2, L1-Leu-3-methyl-Phe-Gln, L1-(R)-|3-Pro-Phe-Gln, and L1-(S)-|3-Pro-Phe-Gln. In embodiments, the compound of formula (I) is selected from L1-Phe-Gln, L1-Leu-Phe-Gln, L1-Leu-Phe-Gln-L2, L1-Leu-3-methyl-Phe-Gln, L1-(R)-p-Pro-Phe-Gln, and L1-(S)-p-Pro-Phe-Gln, optionally wherein L1 is an acyl group or acryloyl and optionally wherein L2 is amino. In embodiments, the compound of formula (I) is selected from L1-Phe-Gln, L1-Leu-Phe-Gln, L1-Leu-Phe-Gln-L2, L1-Leu-3-methyl-Phe-Gln, L1-(R)-p-Pro-Phe-Gln, and L1-(S)-P-Pro-Phe-Gln, optionally wherein L1 is an acyl group or acryloyl and optionally wherein L2 is amino. In embodiments, L1 is an acyl group. In embodiments, L2 is amino. In embodiments, L1 is -C(O)CH3. In embodiments, L1 is -C(O)CH2CH3. In embodiments, L1 is -C(0)CH=CH2. In embodiments, L1 is -0(0)-0=0-0¼ In embodiments, L2 is -NH2. In embodiments, L2 is -OCH3. In embodiments, L2 is methyl. In embodiments, the pharmaceutical composition comprises a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient: NR4aR4b Formula (II) wherein: R1a and R1b are at each occurrence independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl; R2 is selected from hydrogen, unsubstituted or substituted alkyl, and unsubstituted or substituted alkylaryl; X is selected from -CH=CH2, 7 H t Y 0 R8* R8b , d9 , and K Y is selected from -0R3a, and -NR3bR3c; R3a, R3b and R3c are at each occurrence independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkylaryl, and unsubstituted or substituted aryl; optionally wherein R3b and R3c are 5 joined to form an optionally substituted cycloalkyl; R4a and R4b are at each occurrence independently selected from hydrogen, unsubstituted or substituted alkyl, and unsubstituted or substituted alkylaryl, optionally wherein R4a and R4b are joined to form an optionally substituted cycloalkyl; R5 is selected from unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted aryl, and unsubstituted or substituted alkylaryl; R6 is selected from hydrogen, unsubstituted or substituted alkyl, and unsubstituted or substituted alkylaryl; R7 is selected from unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted aryl, and unsubstituted or substituted alkylaryl; R8a and R8b are at each occurrence independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl, optionally wherein R8a and R8b are joined to form an optionally substituted cycloalkyl; R9 is selected from unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted aryl, and unsubstituted or substituted alkylaryl; and R10 is selected from hydrogen, unsubstituted or substituted alkyl, and unsubstituted or substituted alkylaryl. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein Y is selected from -OH, OCH3, NH2, NHMe, and NMe2. 10 In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R1a is hydrogen and R1b is selected from: wherein R11 is selected from hydrogen, unsubstituted or substituted alkyl, and unsubstituted or substituted alkylaryl. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R11 is methyl. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R1a and R1b are at each occurrence independently selected from: In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R4a and R4b are at each occurrence independently selected from hydrogen, methyl, isopropyl, and isobutyl. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R2 is selected from hydrogen, methyl, isopropyl, and isobutyl. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R2 is selected from hydrogen and methyl. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R5 is selected from -CH=CH2, -CH2-CH3, and -C=CCH3. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R6 is selected from hydrogen, and methyl. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R7 is selected from -CH3, -CH=CH2, -CH2-CH3, and -C=CCH3. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R8a is hydrogen and R8b is selected from hydrogen, methyl, isopropyl, and isobutyl. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R8a and R8b are joined to form an optionally substituted cycloalkyl; optionally R8a and R8b are joined to form cyclopropyl. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt 5 thereof, wherein R9 is selected from -CH=CH2, -CH2-CH3, and -C=CCH3. In embodiments, the compound is a compound of formula (II), a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R10 is selected from hydrogen, and methyl. In embodiments, the compound is a compound of formula (Ila), a stereoisomer, or a pharmaceutically acceptable salt thereof: 10 Formula (Ila). In embodiments, the compound is a compound of formula (lib), a stereoisomer, or a pharmaceutically acceptable salt thereof: 15 Formula (lib). In embodiments, the compound is a compound of formula (lie), a stereoisomer, or a pharmaceutically acceptable salt thereof: Formula (lie). In embodiments, the compound is a compound of formula (Illa), a stereoisomer, or a pharmaceutically acceptable salt thereof: Formula (Illa). In embodiments, the compound is a compound of formula (lllb), a stereoisomer, or a pharmaceutically acceptable salt thereof: 10 Formula (lllb). In some embodiments, the compound is a compound of formula (Ila), (lib), (lie), (Illa), (lllb), a stereoisomer, or a pharmaceutically acceptable salt of any one thereof, wherein R1b is selected from: In some embodiments, the compound is a compound of formula (Ila), (lib), (lie), (Illa), (lllb), a stereoisomer, or a 15 pharmaceutically acceptable salt of any one thereof, wherein R2 is selected from hydrogen and methyl. In some embodiments, the compound is a compound of formula (Ila), (lib), (lie), a stereoisomer, or a pharmaceutically In some embodiments, the compound is a compound of formula (Ila), (lib), (lie), (Illa), (lllb), a stereoisomer, or a pharmaceutically acceptable salt of any one thereof, wherein R4a and R4b are at each occurrence independently selected from hydrogen, and methyl. In some embodiments, the compound is a compound of formula (Illa), (lllb), a stereoisomer, or a pharmaceutically acceptable salt of any one thereof, wherein R8b is isobutyl. In some embodiments, the compound is a compound of formula (Ila), (lib), (lie), (Illa), (lllb), a stereoisomer, or a pharmaceutically acceptable salt of any one thereof, wherein R7 is selected from -CH3, -CH=CH2, -CH2-CH3, and -C=CCH3. In some embodiments, the compound is a compound of formula (Ila), (lib), (He), (Illa), (lllb), a stereoisomer, or a pharmaceutically acceptable salt of any one thereof, wherein R5 is selected from -CH=CH2, -CH2-CH3, and -C=CCH3. In some embodiments, the compound is a compound of formula (Ha), (lib), (lie), a stereoisomer, or a pharmaceutically acceptable salt of any one thereof, wherein R6 is selected from hydrogen, and methyl. In some embodiments, the compound is a compound of formula (Ha), (lib), (lie), a stereoisomer, or a pharmaceutically acceptable salt of any one thereof, wherein R9 is selected from -CH=CH2, -CH2-CH3, and -C=CCH3. In some embodiments, the compound is a compound of formula (Ha), (lib), (lie), a stereoisomer, or a pharmaceutically acceptable salt of any one thereof, wherein R10 is selected from hydrogen, and methyl. In embodiments, the compound of formula (I) is a compound of any one of formula SMI-1 to SMI-40: | Formula No. |                     Structure                     | SMI-1 C ‘ r ' N " H £ H „N , ) ■ s. 0 f -.1 c ...OH ) H?NX H 0 f" SMI-2 k 1 N" " H Ns 0 .. .A H » 0 0 H V SMI-3 H 6 N , / x OH O' ^'NH2 h2n v SMI-4 c J ) < " N'" H , H <-Nx 0   l" H ^...OH 5 : / / „,p SMI-5 0 N'At H » C H 7 ° f" ..-A. - 'N > ■■•?••• ...OH > SMI-6 0   * IS          ! H H . . 0 0 f Ax.X ,NH? l"'         V    Z v 2’ 6 H;;N ^..,0 SMI-7 0   * 1 H H v 6 ......~ oA"v o X h2n v;;a SMI-8 0 H H ' H o 0 1..       OH N" v .-1 H - $ SMI-9 0 H f H K ,N 0 0 H2NVv.,.O 0 9 f" SMI-10 / J.x K if 0 -..... / SMI-11 1-0 xl O     \...... ,-¾   1-0 1 o-- / x.....4 o    o SMI-12 X o O--1      £ / ¾¾   1-¾ z / \ ■ \ / d ‘umi < °C, O" SMI-13 9 f H 9 H o ,> O'^xNHa SMI-14 o           K NH; SMI-15 „ .....1.,,1, ,i 1,.. \\    / "y h K '"■ Oh >-N J H       £ \ o^vnh2: SMI-16 43 JL J f J" t / Ss" \ J  H 0 t cf>ih SMI-17 M JO u H 0 SMI-18 jO ^aAAaXh ::            z                           :?            z 6 SMI-19 T     X o     z:— _— SMI-20 r      r~ o    z “■y. / A z— o. r~~\ J SMI-21 ,,   0              0 H ||      ( H |f " TV t O k J O CF4MH SMI-22 iQj H 9 f H C T ' CT ) H SMI-23 X    X o         -z. C   7X2 C:x o / "A \ SMI-24 x      xT P \........ rrr-rrrr.- >>< / XX v-o / SMI-25 k A I a a 'N' Y "V OH \J H 4 Hj SMI-26 SMI-27 SMI-28 SMI-29 SMI-30 SMI-31 (A I ' 0 SMI-32 t A ? r AAAaa h 4 j h i, O SMI-33 1     I) 0                 0 Vx / aa cAAih, SMI-34 0 O zA ? A । / %-'Sr^rN>AoH VJ H 6 i O^NHj SMI-35 (5VjV» O^NH., SMI-36 z X) i A ? <yRivH In embodiments, L1 and / or L2 is or comprises a carrier protein selected from Fc domain, albumin, transferrin, or elastinlike protein, Keyhole Limpet Hemocyanin (KLH), ovalbulin, or a variant thereof. In embodiments, the carrier protein comprises a Fc domain selected from an IgG Fc domain, an IgA Fc domain, an IgM Fc domain, an IgE Fc domain, and 5 an IgD Fc domain. In embodiments, the carrier protein comprises an IgG Fc domain the IgG Fc domain is selected from an IgG 1 Fc domain, an IgG2 Fc domain, an lgG3 Fc domain, and an IgG4 Fc domain. In embodiments, the carrier protein comprises an IgA is selected from an lgA1 Fc domain and an IgA2 Fc domain. In embodiments, L2 is absent. In these embodiments, the compound has the formula: carrier protein-(([Aaa]w)n-[Aaa]x-[Aaa]y-[Aaa]z-Ter), i.e., the carrier protein is linked at the N-terminus of ([Aaa]w)n-[Aaa]x-[Aaa]y-[Aaa]z-Ter). In 10 embodiments, L1 is absent, wherein the compound has the formula: (([Aaa]„)n-[Aaa]x-[Aaa]y-[Aaa]z-Ter)-carrier protein, i.e., the carrier protein is linked at the C-terminus of ([Aaa]w)n-[Aaa]x-[Aaa]y-[Aaa]z-Ter) In embodiments, the carrier protein is linked to ([Aaa]w)n-[Aaa]x-[Aaa]y-[Aaa]z-Ter) via a peptide linker. In embodiments, the peptide linker is rigid or flexible. In embodiments, L1 and / or L2 comprises or further comprises a tag. In embodiments, the tag is selected from hexahistidine tag, FLAG tag, Strep II tag, streptavidin-binding peptide (SBP) tag, calmodulin-binding peptide (CBP), glutathione S-transferase (GST), maltose-binding protein (MBP), S-tag, HA tag, and c-Myc tag. In embodiments, L1 and / or L2 comprises or further comprises a glycosyl moiety. In embodiments, the glycosyl moiety is an N-linked glycosyl moiety. In embodiments, the glycosyl moiety is an O-linked glycosyl moiety. In embodiments, the Trim / inhibitor compound comprises one or more N-linked glycosylation consensus sites and / or O-linked glycosylation consensus sites. In embodiments, the one or more N-linked glycosylation consensus sites and / or 0-linked glycosylation consensus sites are present in ([Aaa]w)n-[Aaa]x-[Aaa]y-[Aaa]z-Ter), the carrier protein, or the tag. In embodiments, the N-linked glycosylation consensus site comprises asparagine (Asn or N)-X-serine (Ser or S) / threonine (Thr or T), wherein X is any amino acid other than proline (Pro or P). In embodiments, the O-linked glycosylation consensus site comprises serine (Ser or S) or threonine (Thr or T). In embodiments, the Trim7 inhibitor compound is biosynthesized as a single polypeptide chain. In embodiments, the Trim / inhibitor compound is biosynthesized from a single open reading frame. In embodiments, the Trim7 inhibitor compound is prepared using an expression system. In embodiments, the expression system is selected from bacterial, yeast, invertebrate (e.g., an insect cell), vertebrate (e.g., a mammalian cell), and plant expression system. In embodiments, one or more of [Aaa]w, [Aaa]x and [Aaa]y are present and are independently selected from non-natural amino acids (e.g., D-amino acids (Daa), and those comprising N-methylation (Nm), Ca-methylation (Cm), amino isobutyric acids (Aib), YjC^NH) reduced amide bonds (Rd), and peptoids (Pp)). In embodiments, L1 and / or L2 comprises or further comprises an alkyl or acyl group that is conjugated to the Trim7 inhibitor compound. In embodiments, L1 and / or L2 comprises an acyl group. In embodiments, the acyl group is an acetyl group. In embodiments, the acyl group is CH3-CH2-C(O)-, CH3-C(0)-, or CH3-C=C-C(0)-. In embodiments, L1 and / or L2 comprises or further comprises a polymer. In embodiments, the polymer is selected from poly(alkylene oxide) (e.g., polyethylene glycol (PEG)), poly(N-vinylpyrrolidone), poly(vinyl alcohol), poly (glycerol), poly(zwitterions), poly(carbonates), polyoxazoline, poly(acryloylmorpholine), poly(oxazolines), poly(sacharrides), and a combination thereof. In embodiments, the polymer is a polyethylene glycol (PEG). In embodiments, one or more amino acids present in the present in ([Aaa]w)n-[Aaa]x-[Aaa]y-[Aaa]z-Ter), the carrier protein, or the tag are PEGylated. In embodiments, one or more PEGylated amino acids comprises Lys and PEGylation is conducted via amine conjugation. In embodiments, one or more PEGylated amino acids comprises Gin and PEGylation is conducted via transglutaminase (TGase) mediated enzymatic conjugation. In embodiments, one or more PEGylated amino acids comprises Cys and PEGylation is conducted via thiol conjugation. In one aspect, the present disclosure relates to a pharmaceutical composition comprising a pharmacologically acceptable carrier and: a polypeptide comprising an amino acid sequence that is at least 90%, or at least 95%, or at least 97%, or at least 98% identical to the amino acid sequence of SEQ ID NO 1 or 2; or a peptide comprising an amino acid sequence of any one of SEQ ID Nos: 3-8 or a variant having about 1, 2, 3, 4, 5 or more amino acid mutations with respect to an amino acid sequence selected from SEQ ID Nos: 3 to 8; or a peptide comprising an amino acid sequence of any one of SEQ ID Nos: 9-12 or a variant having about 1,2, 3, 4, 5 or more amino acid mutations with respect to an amino acid sequence selected from SEQ ID Nos: 9 to 12; or a peptide comprising an amino acid sequence of SEQ ID NO: 15 or a variant having about 1, 2 more amino acid mutations with respect to an amino acid sequence selected from SEQ ID NO: 15. In embodiments, the pharmaceutical composition is formulated for parenteral administration. In embodiments, the pharmaceutical composition is formulated for topical, dermal, intradermal, intramuscular, intraperitoneal, intraarticular, intravenous, subcutaneous, intraarterial or transdermal administration. In embodiments, the pharmaceutical composition is formulated for topical administration. In embodiments, any of the Trim? inhibitors disclosed herein (and / or additional agents) are included various formulations. Any Trim7 inhibitor (and / or additional agents) described herein can take the form of solutions, suspensions, emulsion, drops, tablets, pills, pellets, capsules, capsules containing liquids, powders, sustained-release formulations, suppositories, emulsions, aerosols, sprays, suspensions, or any other form suitable for use. In embodiments, the composition is in the form of a capsule (see, e.g., U.S. Patent No. 5,698,155). Other examples of suitable pharmaceutical excipients are described in Remington’s Pharmaceutical Sciences 1447-1676 (Alfonso R. Gennaro eds., 19th ed. 1995), incorporated herein by reference. In embodiments, the Trim7 inhibitor disclosed herein can possess a sufficiently basic functional group, which can react with an inorganic or organic acid, or a carboxyl group, which can react with an inorganic or organic base, to form a pharmaceutically acceptable salt. A pharmaceutically acceptable acid addition salt is formed from a pharmaceutically acceptable acid, as is well known in the art. Such salts include the pharmaceutically acceptable salts listed in, for example, Journal of Pharmaceutical Science, 66, 2-19 (1977) and The Handbook of Pharmaceutical Salts; Properties, Selection, and Use. P. H. Stahl and C. G. Wermuth (eds.), Verlag, Zurich (Switzerland) 2002, which are hereby incorporated by reference in their entirety. In embodiments, the compositions disclosed herein are in the form of a pharmaceutically acceptable salt. Further, any Trim / inhibitor disclosed herein can be administered to a subject as a component of pharmaceutical composition, that comprises a pharmaceutically acceptable carrier or vehicle. Such pharmaceutical compositions can optionally comprise a suitable amount of a pharmaceutically acceptable excipient so as to provide the form for proper administration. Pharmaceutical excipients can be liquids, such as water and oils, including those of petroleum, animal, vegetable, or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil and the like. The pharmaceutical excipients can be, for example, saline, gum acacia, gelatin, starch paste, talc, keratin, colloidal silica, urea and the like. In addition, auxiliary, stabilizing, thickening, lubricating, and coloring agents can be used. In embodiments, the pharmaceutically acceptable excipients are sterile when administered to a subject. Water is a useful excipient when any agent disclosed herein is administered intravenously. Saline solutions and aqueous dextrose and glycerol solutions can also be employed as liquid excipients, specifically for injectable solutions. Suitable pharmaceutical excipients also include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, ethanol and the like. Any agent disclosed herein, if desired, can also comprise minor amounts of wetting or emulsifying agents, or pH buffering agents. The present disclosure includes the disclosed Trim / inhibitor in various formulations of pharmaceutical composition. Any Trim / inhibitor disclosed herein can take the form of solutions, suspensions, emulsion, drops, tablets, pills, pellets, capsules, capsules containing liquids, powders, sustained-release formulations, suppositories, emulsions, aerosols, sprays, suspensions, or any other form suitable for use. DNA or RNA constructs encoding the protein sequences may also be used. In embodiments, the composition is in the form of a capsule (see, e.g, U.S. Patent No. 5,698,155). Other examples of suitable pharmaceutical excipients are described in Remington’s Pharmaceutical Sciences 144 / -16 / 6 (Alfonso R. Gennaro eds., 19th ed. 1995), incorporated herein by reference. Where necessary, the pharmaceutical compositions comprising the Trim / inhibitor can also include a solubilizing agent. Also, the agents can be delivered with a suitable vehicle or delivery device as known in the art. Combination therapies outlined herein can be co-delivered in a single delivery vehicle or delivery device. Pharmaceutical compositions for administration can optionally include a local anesthetic such as, for example, lignocaine to lessen pain at the site of the injection. The pharmaceutical compositions comprising the Trim / inhibitor of the present disclosure may conveniently be presented in unit dosage forms and may be prepared by any of the methods well known in the art of pharmacy. Such methods generally include the step of bringing therapeutic agents into association with a carrier, which constitutes one or more accessory ingredients. Typically, the pharmaceutical compositions are prepared by uniformly and intimately bringing therapeutic agent into association with a liquid carrier, a finely divided solid carrier, or both, and then, if necessary, shaping the product into dosage forms of the desired formulation (e.g., wet or dry granulation, powder blends, etc., followed by tableting using conventional methods known in the art) In embodiments, any Trim / inhibitor disclosed herein is formulated in accordance with routine procedures as a pharmaceutical composition adapted for a mode of administration disclosed herein. Isolated Polynucleotides In one aspect, the present disclosure relates to an isolated polynucleotide encoding a Trim7 inhibitor compound of any of the embodiments disclosed herein. In embodiments, the isolated polynucleotide is or comprises DNA or RNA. Accordingly, in one aspect, the present disclosure provides an isolated polynucleotide encoding a Trim7 inhibitor compound of the formula (I): L1-(([Aaa]w)n-[Aaa]x-[Aaa]y-[Aaa]z-Ter)-L2. In embodiments, L1 and / or L2 are independently present or absent; and L1 and / or L2, if present, are each independently selected from a carrier protein, a tag, and a chemical group, the chemical group is optionally selected from acryloyl, amino, alkyl, acyl group, a glycosyl moiety, and a polymer. In embodiments, each [Aaa]w is independently selected from an amino acid. In embodiments, Ter is an amino acid. In embodiments, Ter is Gin or Asn. In embodiments, n = 0-20. In embodiments, [Aaa]x is absent or is an amino acid. In embodiments, [Aaa]y is absent or is an amino acid. In embodiments, [Aaa]z is an hydrophobic or aromatic amino acid; and Ter is Gin or Asn. In embodiments, the compound of formula (I) is selected from L1-Phe-Gln, L1-Leu-Phe-Gln, L1-Leu-Phe-Gln-L2, L1-Leu-3-methyl-Phe-Gln, L1-(R)-p-Pro-Phe-Gln, and L1-(S)-|3-Pro-Phe-Gln. In embodiments, the compound of formula (I) is selected from L1-Phe-Gln, L1-Leu-Phe-Gln, L1-Leu-Phe-Gln-L2, L1-Leu-3-methyl-Phe-Gln, L1-(R)-|3-Pro-Phe-Gln, and L1-(S)-|3-Pro-Phe-Gln, optionally wherein L1 is an acyl group or acryloyl and optionally wherein L2 is amino. In embodiments, the compound of formula (I) is selected from L1-Phe-Gln, L1-Leu-Phe-Gln, L1-Leu-Phe-Gln-L2, L1-Leu-3-methyl-Phe-Gln, L1-(R)-P-Pro-Phe-Gln, and L1-(S)-|3-Pro-Phe-Gln, optionally wherein L1 is an acyl group or acryloyl and optionally wherein L2 is amino.. In embodiments, L1 is -0(0)01¼ In embodiments, L1 is -0(0)0^0¼ In embodiments, L1 is -C(O)CH=CH2. In embodiments, L1 is -0(0)-0=0-01¼ In embodiments, L2 is -OCH3. In embodiments, L2 is methyl. In embodiments, the compound of formula (I) is a compound of any one of formula SMI-1 to SMI-40: Formula No. Structure H2NX ,0 ■ y 0 f SMI-1 h A N N" V H 6 '■ X O ;^O 7 zx (  % \ / J .0 SMI-2 ? Th H 6 ........H 0 o H V SMI-3 aq / zx OH 0 :^NH2 i h2n^o SMI-4 9 f H 0 f A H "x$ .„,O SMI-5 p f H H $   - ? f" ... o . SMI-6 0   * IS          ! H H 0 0 f Jl. X ,NH? l"'         V    Z v 2’ 6 H;;N ^..,0 SMI-7 0   * 1 H H v 6 ......~ oA"v o X h2n v;;a SMI-8 0 H H ' H o 0 A ■■■< OH N" v .-1 H - $ ,...,0 SMI-9 0 H f H A .N 0 0 H2N,v.,O 0 9 f" SMI-10 / A K if 0 -..... '''A / SMI-11 SMI-16 X) JL J f J" t / Ss" \ J  H 0 t cf>ih SMI-17 M JO u H 0 SMI-18 jO ^aAAaXh ::            z                           :?            z 6 SMI-19 T     X o     z:— _— SMI-20 r      r~ o    z “■y. / A z— o. r~~\ J SMI-21 ,,   0              0 H ||      ( H |f " YY t O k J O oYh SMI-22 iQj H 9 f H C T ' CT ) H Yh;> SMI-23 X    X o         -z. C   7X2 C:x o / "A \ SMI-24 x      xT P \........ rrr-rrrr.- >>< / XX v-o / SMI-25 k A I a a 'N' Y "V OH \J H 4 (YY Hj SMI-26 SMI-27 SMI-28 SMI-29 SMI-30 SMI-31 (A I ' 0 SMI-32 t A ? r AAAaa h 4 j h i, O SMI-33 1     I) 0                 0 Vx / aa cAAih, SMI-34 0 O zA ? A । / %-'Sr^rN>AoH VJ H 6 i O^NHj SMI-35 (5VjV» O^NH., SMI-36 z X) i A ? <yRivH In embodiments, the polynucleotide encodes a Trim? inhibitor compound comprising Ter of any of the embodiments disclosed herein. In embodiments, the polynucleotide encodes a Trim? inhibitor compound comprising [Aaa]z of any of the embodiments disclosed herein. In embodiments, the polynucleotide encodes a Trim? inhibitor compound 5 comprising [Aaa]y of any of the embodiments disclosed herein. In embodiments, the polynucleotide encodes a Trim? inhibitor compound comprising [Aaa]x of any of the embodiments disclosed herein. In embodiments, the polynucleotide encodes a Trim? inhibitor compound comprising [Aaa]w of any of the embodiments disclosed herein. In embodiments, the polynucleotide encodes a Trim? inhibitor compound comprising L of any of the embodiments disclosed herein. In embodiments, the polynucleotide is DNA. In embodiments, the polynucleotide comprises control element. 10 In one aspect, the present disclosure provides a vector comprising the isolated polynucleotide of any of embodiments disclosed herein. A vector generally comprises an isolated nucleic acid and which can be used to deliver the isolated nucleic acid to the interior of a cell. Numerous vectors are known in the art including, but not limited to, linear polynucleotides, polynucleotides associated with ionic or amphiphilic Trim7 inhibitor compounds, plasmids, and viruses. In embodiments, the vector is a viral vector. Exemplary vectors include autonomously replicating plasmids or a virus (e.g. ,AAV vectors). The term should also be construed to include non-plasmid and non-viral Trim7 inhibitor compounds thatfacilitate transfer of nucleic acid into cells, such as, for example, polylysine Trim7 inhibitor compounds, liposomes, and the like. Examples of viral vectors include, but are not limited to, adenoviral vectors, adeno-associated virus vectors, retroviral vectors, and the like. In embodiments, the expression vector comprises the nucleic acid encoding the Trim7 inhibitor compounds operably linked to an expression control region that is functional in the host cell. The expression control region is capable of driving expression of the operably linked encoding nucleic acid such that the Trim7 inhibitor compounds is produced in a desired host cell transformed with the expression vector. Expression control regions are regulatory polynucleotides (sometimes referred to herein as elements), such as promoters and enhancers, that influence expression of an operably linked nucleic acid. An expression control region of an expression vector is capable of expressing operably linked encoding nucleic acid in a desired host cell. In an embodiment, the expression control region confers regulatable expression to an operably linked nucleic acid. A signal (sometimes referred to as a stimulus) can increase or decrease expression of a nucleic acid operably linked to such an expression control region. Such expression control regions that increase expression in response to a signal are often referred to as inducible. Such expression control regions that decrease expression in response to a signal are often referred to as repressible. In embodiments, the Trim7 inhibitor compounds expression is inducible or repressible. Typically, the amount of increase or decrease conferred by such elements is proportional to the amount of signal present; the greater the amount of signal, the greater the increase or decrease in expression. In one aspect, the present disclosure provides a vector comprising the isolated polynucleotide of any one of the embodiments disclosed herein. In embodiments, the Trim7 inhibitor compound can be provided as an expression vector. In embodiments, the expression vector is a DNA expression vector or an RNA expression vector. In embodiments, the expression vector is a viral expression vector. In embodiments, the expression vector is a non-viral expression vector (without limitation, e.g. a plasmid). In embodiments, the present non-viral vectors are linear or circular DNA molecules that comprise a polynucleotide encoding a polypeptide and is operably linked to control sequences, wherein the control sequences provide for expression of the polynucleotide encoding the polypeptide. In embodiments, the non-viral vector comprises a promoter sequence, and transcriptional and translational stop signal sequences. In embodiments, the expression vector may include, among others, chromosomal and episomal vectors, e.g., vectors derived from bacterial plasmids, from transposons, from yeast episomes, from insertion elements, from yeast chromosomal elements, and vectors derived from combinations thereof. The present constructs may contain control regions that regulate as well as engender expression. A vector generally comprises an isolated nucleic acid and which can be used to deliver the isolated nucleic acid to the interior of a cell. Numerous vectors are known in the art including, but not limited to, linear polynucleotides, polynucleotides associated with ionic or amphiphilic Trim? inhibitor compounds, plasmids, and viruses. In embodiments, the expression vector is an autonomously replicating plasmid or a virus (e.g. AAV vectors). In embodiments, the expression vector is non-plasmid and non-viral Trim? inhibitor compounds that facilitate transfer of nucleic acid into cells, such as, for example, polylysine Trim? inhibitor compounds, liposomes, and the like. Examples of viral vectors include, but are not limited to, adenoviral vectors, adeno-associated virus vectors, retroviral vectors, and the like. In embodiments, the polynucleotide or cell therapy may employ expression vectors, which comprise the nucleic acid encoding the Trim? inhibitor compound operably linked to an expression control region that is functional in the host cell. The expression control region is capable of driving expression of the operably linked encoding nucleic acid such that the Trim7 inhibitor compound is produced in a human cell transformed with the expression vector. Expression control regions are regulatory polynucleotides (sometimes referred to herein as elements), such as promoters and enhancers, that influence expression of an operably linked nucleic acid. An expression control region of an expression vector is capable of expressing operably linked encoding nucleic acid in a human cell. In an embodiment, the expression control region confers regulatable expression to an operably linked nucleic acid. A signal (sometimes referred to as a stimulus) can increase or decrease expression of a nucleic acid operably linked to such an expression control region. Such expression control regions that increase expression in response to a signal are often referred to as inducible. Such expression control regions that decrease expression in response to a signal are often referred to as repressible. In various embodiments, the Trim / inhibitor compound expression is inducible or repressible. Typically, the amount of increase or decrease conferred by such elements is proportional to the amount of signal present; the greater the amount of signal, the greater the increase or decrease in expression. Expression systems functional in human cells are well known in the art, and include viral systems. Generally, a promoter functional in a human cell is any DNA sequence capable of binding mammalian RNA polymerase and initiating the downstream (31) transcription of a coding sequence into mRNA. A promoter will have a transcription-initiating region, which is usually placed proximal to the 5' end of the coding sequence, and typically a TATA box located 25-30 base pairs upstream of the transcription initiation site. The TATA box is thought to direct RNA polymerase II to begin RNA synthesis at the correct site. A promoter will also typically contain an upstream promoter element (enhancer element), typically located within 100 to 200 base pairs upstream of the TATA box. An upstream promoter element determines the rate at which transcription is initiated and can act in either orientation. Of particular use as promoters are the promoters from mammalian viral genes, since the viral genes are often highly expressed and have a broad host range. Examples include the SV40 early promoter, mouse mammary tumor virus LTR promoter, adenovirus major late promoter, herpes simplex virus promoter, and the CIW promoter. Where appropriate, gene delivery agents such as, e.g., integration sequences can also be employed. Numerous integration sequences are known in the art (see, e.g., Nunes-Duby et al., Nucleic Acids Res. 26:391-406, 1998; Sadwoski, J. Bacteriol., 165:341-357,1986; Bestor, Cell, 122(3):322-325, 2005; Plasterk etal., TIG 15:326-332,1999; Kootstra et al., Ann. Rev. Pharm. Toxicol., 43:413-439, 2003). These include recombinases and transposases. Examples include Cre (Sternberg and Hamilton, J. Mol. Biol., 150:467-486, 1981), lambda (Nash, Nature, 247, 543545, 1974), Flp (Broach, etal., Cell, 29:227-234, 1982), R (Matsuzaki, etal., J. Bacteriology, 172:610-618, 1990), cpC31 (see, e.g., Groth etal., J. Mol. Biol. 335:667-678, 2004), sleeping beauty, transposases of the mariner family, and components for integrating viruses such as AAV, retroviruses, and antiviruses having components that provide for virus integration such as the LTR sequences of retroviruses or lentivirus and the ITR sequences of AAV (Kootstra et al., Ann. Rev. Pharm. Toxicol., 43:413-439, 2003). In addition, direct and targeted genetic integration strategies may be used to insert nucleic acid sequences including CRISPR / CAS9, zinc finger, TALEN, and meganuclease geneediting technologies. In embodiments, host cells are transformed with the DNA molecule or vector. Host cells include cells used for recombinant protein expression, include yeast cell systems, bacterial cell systems, and eukaryotic cell systems including mammalian cells {e.g., CHO cells) and other cell systems conventionally employed. In embodiments that do not require PEGylation, the cell harboring the polynucleotide encoding the Trim7 inhibitor compounds can be a cell employed for cell therapy, such as a T cell or stem cell, to thereby produce the Trim7 inhibitor compounds in vivo. Various host cells can be used as recombinant protein expression systems according to the disclosure. In embodiments, the host cell may be a microorganism, a fungal cell, an algal cell, or a plant cell. In embodiments, the host cell is a microbial cell. The microbial host cell In embodiments may be prokaryotic or eukaryotic. In embodiments, the microbial host cell is a bacteria, and which can be optionally selected from Escherichia spp., Bacillus spp., Corynebacterium spp., Lactococcus spp., and Pseudomonas spp. For example, In embodiments, the bacterial host cell is a species selected from Escherichia coli, Bacillus subtilis, Corynebacterium glutamicum, Pseudomonas fluorescens, and Lactococcus lactis. In embodiments, the bacterial host cell is E. coli. Alternatively, the microbial cell may be a yeast cell, such as but not limited to a species of Saccharomyces, Pichia, Komagataella sp., Kluyveromyces, or Yarrowia, including Saccharomyces cerevisiae, Pichia pastoris, and Yarrowia lipolytica. In embodiments, the host cell is a yeast cell selected from Pichiapastoris, Saccharomyces cerevisiae, Komagataella sp., Kluyveromyces lactis, and Yarrowia lipolytica. In embodiments, the host cell is a fungal cell selected from Aspergillus niger, Trichoderma reesei, and Myceliophthora thermophila. In embodiments, the host cell is Pichia pastoris. In embodiments, the host cell is a mammalian cell. In embodiments, the host cell is a mammalian cell line. In embodiments, the cell line is selected from NS0 murine myeloma cells, PER.C6 human cells, and Chinese hamster ovary (CHO) cells, baby hamster kidney (BHK21) cells, murine myeloma Sp2 / 0 cells, human embryonic kidney 293 (HEK293) cells, HT-1080 cells, Hela cells, CAP cells, HKB-11 cells, HuH-7 cells, and a derivative thereof. In embodiments, the cell line is selected from CHO DUXB11, CHO DG44, CH0K1, ExpiCHO and Expi293. In embodiments, the host cell is an insect cell line. In embodiments, the cell line is Sf9 or a derivative thereof. In one aspect, the present disclosure provides a host cell comprising the vector of any of the embodiments disclosed herein. A host cell comprising the mmRNA of any of the embodiments disclosed herein. In embodiments, the nucleic acid is RNA. In embodiments, the RNA is an mRNA. In embodiments, the mRNA is a modified mRNA (mmRNA). In embodiments, the polynucleotide is mRNA or a modified mRNA (mmRNA). The modified polypeptide may include a polynucleotide modification including, but not limited to, a nucleoside modification. In embodiments, the polynucleotide is an mmRNA. In embodiments, the mmRNA comprises one or more nucleoside modifications. In embodiments, the nucleoside modifications are selected from pyridin-4-one ribonucleoside, 5-aza-uridine, 2-thio-5-aza-uridine, 2-thiouridine, pseudouridine, 4-thio-pseudouridine, 2-thio-pseudouridine, 5-hydroxyuridine, 3-methyluridine, 5-carboxymethyl-uridine, 1-carboxymethyl-pseudouridine, 5-propynyl-uridine, 1-propynyl-pseudouridine, 5-taurinomethyluridine, 1-taurinomethyl-pseudouridine, 5-taurinomethyl-2-thio-uridine, 1-taurinomethyl-4-thio-uridine, 5-methyl-uridine, 1-methyl-pseudouridine, 4-thio-1-methyl-pseudouridine, 2-thio-1-methyl-pseudouridine, 1-methyl-1-deaza-pseudouridine, 2-thio-1 -methyl-1 -deaza-pseudouridine, dihydrouridine, dihydropseudouridine, 2-thio-dihydrouridine, 2-thio-dihydropseudouridine, 2-methoxyuridine, 2-methoxy-4-thio-uridine, 4-methoxy-pseudouridine, 4-methoxy-2-thio-pseudouridine, 5-aza-cytidine, pseudoisocytidine, 3-methyl-cytidine, N4-acetylcytidine, 5-formylcytidine, N4-methylcytidine, 5-hydroxymethylcytidine, 1-methyl-pseudoisocytidine, pyrrolo-cytidine, pyrrolo-pseudoisocytidine, 2-thio-cytidine, 2-thio-5-methyl-cytidine, 4-thio-pseudoisocytidine, 4-thio-1-methyl-pseudoisocytidine, 4-thio-1-methyl-1-deaza-pseudoisocytidine, 1-methyl-1-deaza-pseudoisocytidine, zebularine, 5-aza-zebularine, 5-methyl-zebularine, 5-aza-2-thio-zebularine, 2-thio-zebularine, 2-methoxy-cytidine, 2-methoxy-5-methyl-cytidine, 4-methoxy-pseudoisocytidine, 4-methoxy-1-methyl-pseudoisocytidine, 2-aminopurine, 2, 6-diaminopurine, 7-deaza-adenine, 7-deaza-8-aza-adenine, 7-deaza-2-aminopurine, 7-deaza-8-aza-2-aminopurine, 7-deaza-2,6-diaminopurine, 7-deaza-8-aza-2,6-diaminopurine, 1-methyl adenosine, N6-methyladenosine, N6-isopentenyladenosine, N6-(cis-hydroxyisopentenyl)adenosine, 2-methylthio-N6-(cis-hydroxyisopentenyl) adenosine, N6-glycinylcarbamoyladenosine, N6-threonylcarbamoyladenosine, 2-methylthio-N6-threonyl carbamoyladenosine, N6,N6-dimethyladenosine, 7-methyladenine, 2-methylthio-adenine, and 2-methoxy-adenine, inosine, 1-methyl-inosine, wyosine, wybutosine, 7-deaza-guanosine, 7-deaza-8-aza-guanosine, 6-thio-guanosine, 6-thio-7-deaza-guanosine, 6-thio-7-deaza-8-aza-guanosine, 7-methyl-guanosine, 6-thio-7-methyl-guanosine, 7-methylinosine, 6-methoxy-guanosine, 1-methylguanosine, N2-methylguanosine, N2,N2-dimethylguanosine, 8-oxo-guanosine, 7-methyl-8-oxo-guanosine, 1-methyl-6-thio-guanosine, N2-methyl-6-thio-guanosine, and N2,N2-dimethyl-6-thio-guanosine, and combinations thereof. Further examples of modified nucleotides and modified nucleotide combinations are disclosed in US Patent Nos. 8,710,200; 8,822,663; 8,999,380; 9,181,319 ; 9,254,311; 9,334,328; 9,464,124; 9,950,068; 10,626,400; 10,808,242; 11,020,477, and WO 2014 / 028429, the entire contents of which are hereby incorporated by reference. Administration, Dosing, and Treatment Regimens In one embodiment, any Trim7 inhibitor (and / or additional agents) described herein is formulated in accordance with routine procedures as a composition adapted for a mode of administration described herein. Routes of administration include, for example: intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal, epidural, oral, sublingual, intranasal, intracerebral, intravaginal, transdermal, rectally, by inhalation, or topically, particularly to the ears, nose, eyes, or skin. In embodiments, the administering is effected orally or by parenteral injection. In most instances, administration results in the release of any agent described herein into the bloodstream. Any Trim7 inhibitor (and / or additional agents) described herein can be administered orally. Such Trim7 inhibitors (and / or additional agents) can also be administered by any other convenient route, for example, by intravenous infusion or bolus injection, by absorption through epithelial or mucocutaneous linings (e.g., oral mucosa, rectal and intestinal mucosa, etc.) and can be administered together with another biologically active agent. Administration can be systemic or local. Various delivery systems are known, e.g., encapsulation in liposomes, microparticles, microcapsules, capsules, etc., and can be used to administer. In specific embodiments, it may be desirable to administer locally to the area in need of treatment. In one embodiment, for instance in the treatment of cancer, the Trim7 inhibitor (and / or additional agents) are administered in the tumor microenvironment (e.g., cells, molecules, extracellular matrix and / or blood vessels that surround and / or feed a tumor cell, inclusive of, for example, tumor vasculature; tumor-infiltrating lymphocytes; fibroblast reticular cells; endothelial progenitor cells (EPC); cancer-associated fibroblasts; pericytes; other stromal cells; components of the extracellular matrix (ECM); dendritic cells; antigen presenting cells; T-cells; regulatory T cells; macrophages; neutrophils; and other immune cells located proximal to a tumor) or lymph node and / or targeted to the tumor microenvironment or lymph node. In various embodiments, for instance in the treatment of cancer, the Trim7 inhibitor (and / or additional agents) are administered intratumorally. Dosage forms suitable for parenteral administration (e.g., intravenous, intramuscular, intraperitoneal, subcutaneous and intra-articular injection and infusion) include, for example, solutions, suspensions, dispersions, emulsions, and the like. They may also be manufactured in the form of sterile solid compositions (e.g., lyophilized composition), which can be dissolved or suspended in sterile injectable medium immediately before use. They may contain, for example, suspending or dispersing agents known in the art. The dosage of any Trim7 inhibitor (and / or additional agents) described herein as well as the dosing schedule can depend on various parameters, including, but not limited to, the disease being treated, the subject's general health, and the administering physician's discretion. Any Trim7 inhibitor described herein, can be administered prior to (e.g., 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks before), concurrently with, or subsequent to (e.g., 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks after) the administration of an additional agent, to a subject in need thereof. In various embodiments any Trim7 inhibitor and additional agent described herein are administered 1 minute apart, 10 minutes apart, 30 minutes apart, less than 1 hour apart, 1 hour apart, 1 hour to 2 hours apart, 2 hours to 3 hours apart, 3 hours to 4 hours apart, 4 hours to 5 hours apart, 5 hours to 6 hours apart, 6 hours to 7 hours apart, 7 hours to 8 hours apart, 8 hours to 9 hours apart, 9 hours to 10 hours apart, 10 hours to 11 hours apart, 11 hours to 12 hours apart, 1 day apart, 2 days apart, 3 days apart, 4 days apart, 5 days apart, 6 days apart, 1 week apart, 2 weeks apart, 3 weeks apart, or 4 weeks apart. In various embodiments, the current disclosure relates to the co-administration of a Trim7 inhibitor which induces an innate immune response and another Trim / inhibitor which induces an adaptive immune response. In such embodiments, the Trim7 inhibitor which induces an innate immune response may be administered before, concurrently with, or subsequent to administration of the Trim7 inhibitor which induces an adaptive immune response. For example, the Trim7 inhibitors may be administered 1 minute apart, 10 minutes apart, 30 minutes apart, less than 1 hour apart, 1 hour apart, 1 hour to 2 hours apart, 2 hours to 3 hours apart, 3 hours to 4 hours apart, 4 hours to 5 hours apart, 5 hours to 6 hours apart, 6 hours to 7 hours apart, 7 hours to 8 hours apart, 8 hours to 9 hours apart, 9 hours to 10 hours apart, 10 hours to 11 hours apart, 11 hours to 12 hours apart, 1 day apart, 2 days apart, 3 days apart, 4 days apart, 5 days apart, 6 days apart, 1 week apart, 2 weeks apart, 3 weeks apart, or 4 weeks apart. In an illustrative embodiment, the Trim7 inhibitor which induces an innate immune response and the Trim7 inhibitor which induces an adaptive response are administered 1 week apart, or administered on alternate weeks ( / .e., administration of the Trim7 inhibitor inducing an innate immune response is followed 1 week later with administration of the Trim7 inhibitor which induces an adaptive immune response and so forth). The dosage of any Trim7 inhibitor (and / or additional agents) described herein can depend on several factors including the severity of the condition, whether the condition is to be treated or prevented, and the age, weight, and health of the subject to be treated. Additionally, pharmacogenomic (the effect of genotype on the pharmacokinetic, pharmacodynamic or efficacy profile of a therapeutic) information about a particular subject may affect dosage used. Furthermore, the exact individual dosagescan be adjusted somewhat depending on a variety of factors, including the specific combination of the agents being administered, the time of administration, the route of administration, the nature of the formulation, the rate of excretion, the particular disease being treated, the severity of the disorder, and the anatomical location of the disorder. Some variations in the dosage can be expected. For administration of any Trim7 inhibitor (and / or additional agents) described herein by parenteral injection, the dosage may be about 0.1 mg to about 250 mg per day, about 1 mg to about 20 mg per day, or about 3 mg to about 5 mg per day. Generally, when orally or parenterally administered, the dosage of any agent described herein may be about 0.1 mg to about 1500 mg per day, or about 0.5 mg to about 10 mg per day, or about 0.5 mg to about 5 mg per day, or about 200 to about 1,200 mg per day (e.g., about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, about 1,000 mg, about 1,100 mg, about 1,200 mg per day). In embodiments, administration of the Trim7 inhibitor (and / or additional agents) described herein is by parenteral injection at a dosage of about 0.1 mg to about 1500 mg per treatment, or about 0.5 mg to about 10 mg per treatment, or about 0.5 mg to about 5 mg per treatment, or about 200 to about 1,200 mg per treatment (e.g., about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, about 1,000 mg, about 1,100 mg, about 1,200 mg per treatment). In embodiments, a suitable dosage of the Trim7 inhibitor (and / or additional agents) is in a range of about 0.01 mg / kg to about 100 mg / kg of body weight ,or about 0.01 mg / kg to about 10 mg / kg of body weight of the subject, for example, about 0.01 mg / kg, about 0.02 mg / kg, about 0.03 mg / kg, about 0.04 mg / kg, about 0.05 mg / kg, about 0.06 mg / kg, about 0.07 mg / kg, about 0.08 mg / kg, about 0.09 mg / kg, about 0.1 mg / kg, about 0.2 mg / kg, about 0.3 mg / kg, about 0.4 mg / kg, about 0.5 mg / kg, about 0.6 mg / kg, about 0.7 mg / kg, about 0.8 mg / kg, about 0.9 mg / kg, about 1 mg / kg, about 1.1 mg / kg, about 1.2 mg / kg, about 1.3 mg / kg, about 1.4 mg / kg, about 1.5 mg / kg, about 1.6 mg / kg, about 1.7 mg / kg, about 1.8 mg / kg, 1.9 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg body weight, inclusive of all values and ranges therebetween. In another embodiment, delivery can be in a vesicle, in particular a liposome (see Langer, 1990, Science 249:15271533; Treat et al., in Liposomes in the Therapy of Infectious Disease and Cancer, Lopez-Berestein and Fidler (eds.), Liss, New York, pp. 353-365 (1989). Any Trim7 inhibitor (and / or additional agents) described herein can be administered by controlled-release or sustained-release means or by delivery devices that are well known to those of ordinary skill in the art. Examples include, but are not limited to, those described in U.S. Patent Nos. 3,845,770; 3,916,899; 3,536,809; 3,598,123; 4,008,719; 5,674,533; 5,059,595; 5,591,767; 5,120,548; 5,073,543; 5,639,476; 5,354,556; and 5,733,556, each of which is incorporated herein by reference in its entirety. Such dosage forms can be useful for providing controlled- or sustained-release of one or more active ingredients using, for example, hydropropylmethyl cellulose, other polymer matrices, gels, permeable membranes, osmotic systems, multilayer coatings, microparticles, liposomes, microspheres, or a combination thereof to provide the desired release profile in varying proportions. Controlled- or sustained-release of an active ingredient can be stimulated by various conditions, including but not limited to, changes in pH, changes in temperature, stimulation by an appropriate wavelength of light, concentration or availability of enzymes, concentration or availability of water, or other physiological conditions or compounds. In another embodiment, polymeric materials can be used (see Medical Applications of Controlled Release, Langer and Wise (eds.), CRC Pres., Boca Raton, Florida (1974); Controlled Drug Bioavailability, Drug Product Design and Performance, Smolen and Ball (eds.), Wiley, New York (1984); Ranger and Peppas, 1983, J. Macromol. Sci. Rev. Macromol. Chem. 23:61; seea / soLevy etal., 1985, Science228:190; During etal., 1989, Ann. Neurol. 25:351; Howard etal., 1989, J. Neurosurg. 71:105). In another embodiment, a controlled-release system can be placed in proximity of the target area to be treated, thus requiring only a fraction of the systemic dose (see, e.g., Goodson, in Medical Applications of Controlled Release, supra, vol. 2, pp. 115-138 (1984)). Other controlled-release systems discussed in the review by Langer, 1990, Science 249:1527-1533) may be used. Administration of any Trim / inhibitor (and / or additional agents) described herein can, independently, be one to four times daily or one to four times per month or one to six times per year or once every two, three, four or five years. Administration can be for the duration of one day or one month, two months, three months, six months, one year, two years, three years, and may even be for the life of the subject. The dosage regimen utilizing any Trim7 inhibitor (and / or additional agents) described herein can be selected in accordance with a variety of factors including type, species, age, weight, sex and medical condition of the subject; the severity of the condition to be treated; the route of administration; the renal or hepatic function of the subject; the pharmacogenomic makeup of the individual; and the specific compound of the disclosure employed. Any Trim7 inhibitor (and / or additional agents) described herein can be administered in a single daily dose, or the total daily dosage can be administered in divided doses of two, three or four times daily. Furthermore, any Trim7 inhibitor (and / or additional agents) described herein can be administered continuously rather than intermittently throughout the dosage regimen. Diseases; Methods of Treatment, and Patient Selections In one aspect, the present disclosure relates to a method for treating a cancer, an infectious disease, an inflammatory disease in a subject in need thereof, the method comprising administering to the subject the pharmaceutical composition of any of the embodiments disclosed herein. In embodiments, the cancer is selected from a basal cell carcinoma, biliary tract cancer; bladder cancer; bone cancer; brain and central nervous system cancer; breast cancer; cancer of the peritoneum; cervical cancer; choriocarcinoma; colon and rectum cancer; connective tissue cancer; cancer of the digestive system; endometrial cancer; esophageal cancer; eye cancer; cancer of the head and neck; gastric cancer (including gastrointestinal cancer); glioblastoma; hepatic carcinoma; hepatoma; intra-epithelial neoplasm; kidney or renal cancer; larynx cancer; leukemia; liver cancer; lung cancer {e.g., small-cell lung cancer, non-small cell lung cancer, adenocarcinoma of the lung, and squamous carcinoma of the lung); melanoma; myeloma; neuroblastoma; oral cavity cancer (lip, tongue, mouth, and pharynx); ovarian cancer; pancreatic cancer; prostate cancer; retinoblastoma; rhabdomyosarcoma; rectal cancer; cancer of the respiratory system; salivary gland carcinoma; sarcoma; skin cancer; squamous cell cancer; stomach cancer; testicular cancer; thyroid cancer; uterine or endometrial cancer; cancer of the urinary system; vulval cancer; lymphoma including Hodgkin's and non-Hodgkin's lymphoma, as well as B-cell lymphoma (including low grade / follicular non-Hodgkin's lymphoma (NHL); small lymphocytic (SL) NHL; intermediate grade / follicular NHL; intermediate grade diffuse NHL; high grade immunoblastic NHL; high grade lymphoblastic NHL; high grade small non-cleaved cell NHL; bulky disease NHL; mantle cell lymphoma; AIDS-related lymphoma; and Waldenstrom's Macroglobulinemia; chronic lymphocytic leukemia (CLL); acute lymphoblastic leukemia (ALL); Hairy cell leukemia; chronic myeloblastic leukemia; as well as other carcinomas and sarcomas; and posttransplant lymphoproliferative disorder (PTLD), as well as abnormal vascular proliferation associated with phakomatoses, edema (such as that associated with brain tumors), and Meigs’ syndrome. In embodiments, the cancer is a hematologic cancer selected from the group consisting of chronic lymphocytic leukemia (CLL), acute leukemias, acute lymphoid leukemia (ALL), B-cell acute lymphoid leukemia (B-ALL), T-cell acute lymphoid leukemia (T-ALL), chronic myelogenous leukemia (CML), B cell prolymphocytic leukemia, blastic plasmacytoid dendritic cell neoplasm, Burkitt's lymphoma, diffuse large B cell lymphoma, follicular lymphoma, hairy cell leukemia, small cell- or a large cell-follicular lymphoma, malignant lymphoproliferative conditions, MALT lymphoma, mantle cell lymphoma, marginal zone lymphoma, multiple myeloma, myelodysplasia and myelodysplastic syndrome, non-Hodgkin’s lymphoma, Hodgkin's lymphoma, plasmablastic lymphoma, plasmacytoid dendritic cell neoplasm, Waldenstrom macroglobulinemia, and pre-leukemia, or a combination thereof. In embodiments, the cancer is resistant to an anti-checkpoint agent. In embodiments, the anti-checkpoint agent is an antibody. In embodiments, the anti-checkpoint agent an anti-PD-1, antiPD-L 1. anti-PD-L2, and / or anti-CTLAantibody. In embodiments, the antibody is selected from nivolumab (OPDIVO), pembrolizumab (KEYTRUDA), pidilizumab (CT-011, CURE TECH), MK-3475 (MERCK), BMS 936559, MPDL328OA (ROCHE), Cemiplimab (LIBTAYO), Atezolizumab (TECENTRIQ), Avelumab (BAVENCIO), and Durvalumab (imfinzi). In embodiments, the infectious disease is a viral infection. In embodiments, the viral infection is caused by a virus selected from papilloma virus, herpes simplex virus (HSV), human immunodeficiency virus (HIV), hepatitis virus, Zika virus, Yellow Fever Virus, West Nile virus, Dengue virus, Japanese Encephalitis Virus, St. Louis Encephalitis Virus, Hepatitis C Virus, poliovirus, rhinovirus, enterovirus, coxsackievirus, influenza virus, lentivirus, respiratory syncytial virus, a human parainfluenza virus, rubulavirus (e.g., mumps virus), measles virus, human metapneumovirus, hantavirus, rotavirus, norovirus, and SARS virus (e.g., SARS-CoV-2). In embodiments, the inflammatory disease is an autoimmune disease or condition, selected from multiple sclerosis, diabetes mellitus, lupus, celiac disease, Crohn's disease, ulcerative colitis, Guillain-Barre syndrome, scleroderms, Goodpasture's syndrome, Wegener's granulomatosis, autoimmune epilepsy, Rasmussen's encephalitis, Primary biliary sclerosis, Sclerosing cholangitis, Autoimmune hepatitis, Addison's disease, Hashimoto's thyroiditis, Fibromyalgia, Menier's syndrome; transplantation rejection {e.g, prevention of allograft rejection) pernicious anemia, rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, Sjogren's syndrome, lupus erythematosus, multiple sclerosis, myasthenia gravis, Reiter's syndrome, Grave's disease, and other autoimmune disease. In one aspect, the present disclosure relates to a method for treating an anti-checkpoint agent-resistant cancer in a subject in need thereof, the method comprising administering to the subject the pharmaceutical composition of any one of embodiments disclosed herein. In embodiments, the anti-checkpoint agent is an antibody. In embodiments, the antibody is selected from nivolumab (OPDIVO), pembrolizumab (KEYTRUDA), pidilizumab (CT-011, CURE TECH), MK-3475 (MERCK), BMS 936559, MPDL328OA (ROCHE), Cemiplimab (LIBTAYO), Atezolizumab (TECENTRIQ), Avelumab (BAVENCIO), and Durvalumab (imfinzi). In one aspect, the present disclosure relates to methods of treating viral infections including, without limitation, acute or chronic viral infections, for example, of the respiratory tract, of papilloma virus infections, of herpes simplex virus (HSV) infection, of human immunodeficiency virus (HIV) infection, and of viral infection of internal organs such as infection with hepatitis viruses. In embodiments, the viral infection is caused by a virus of family Flaviviridae. In embodiments, the virus of family Flaviviridae is selected from Zika virus, Yellow Fever Virus, West Nile virus, Dengue virus, Japanese Encephalitis Virus, St. Louis Encephalitis Virus, and Hepatitis C Virus. In embodiments, the viral infection is caused by a virus of family Picornaviridae, e.g, poliovirus, rhinovirus, enterovirus, coxsackievirus. In embodiments, the viral infection is caused by a member of Orthomyxoviridae, e.g, an influenza virus. In embodiments, the viral infection is caused by a member of Retroviridae, e.g, a lentivirus. In embodiments, the viral infection is caused by a member of Paramyxoviridae, e.g, respiratory syncytial virus, a human parainfluenza virus, rubulavirus {e.g, mumps virus), measles virus, and human metapneumovirus. In embodiments, the viral infection is caused by a member of Bunyaviridae, e.g., hantavirus. In embodiments, the viral infection is caused by a member of Reoviridae, e.g., a rotavirus. In one aspect, the present disclosure relates to methods of treating parasitic infections such as protozoan or helminths infections. In embodiments, the parasitic infection is by a protozoan parasite. In embodiments, the oritiziab parasite is selected from intestinal protozoa, tissue protozoa, or blood protozoa. Illustrative protozoan parasites include, but are not limited to, Entamoeba hystolytica, Giardia lamblia, Cryptosporidium muris, Trypanosomatida gambiense, Trypanosomatida rhodesiense, Trypanosomatida crusi, Leishmania mexicana, Leishmania braziliensis, Leishmania tropica, Leishmania donovani, Toxoplasma gondii, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae, Plasmodium falciparum, Trichomonas vaginalis, and Histomonas meleagridis. In embodiments, the parasitic infection is by a helminthic parasite such as nematodes {e.g, Adenophorea). In embodiments, the parasite is selected from Secementea {e.g, Trichuris trichiura, Ascaris lumbricoides, Enterobius vermicularis, Ancylostoma duodenale, Necator americanus, Strongyloides stercoralis, Wuchereria bancrofti, Dracunculus medinensis). In embodiments, the parasite is selected from trematodes (e.g. blood flukes, liver flukes, intestinal flukes, and lung flukes). In embodiments, the parasite is selected from: Schistosoma mansoni, Schistosoma haematobium, Schistosoma japonicum, Fasciola hepatica, Fasciola gigantica, Heterophyes, Paragonimus westermani. In embodiments, the parasite is selected from cestodes (e.g, Taenia solium, Taenia saginata, Hymenolepis nana, Echinococcus granulosus). In one aspect, the present disclosure relates to methods of treating bacterial infections. In embodiments, the bacterial infection is by gram-positive bacteria, gram-negative bacteria, aerobic and / or anaerobic bacteria. In embodiments, the bacteria is selected from, but not limited to, Staphylococcus, Lactobacillus, Streptococcus, Sarcina, Escherichia, Enterobacter, Klebsiella, Pseudomonas, Acinetobacter, Mycobacterium, Proteus, Campylobacter, Citrobacter, Nisseria, Baccillus, Bacteroides, Peptococcus, Clostridium, Salmonella, Shigella, Serratia, Haemophilus, Brucella and other organisms. In embodiments, the bacteria is selected from, but not limited to, Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas acidovorans, Pseudomonas alcaligenes, Pseudomonas putida, Stenotrophomonas maltophilia, Burkholderia cepacia, Aeromonas hydrophilia, Escherichia coli, Citrobacter freundii, Salmonella typhimurium, Salmonella typhi, Salmonella paratyphi, Salmonella enteritidis, Shigella dysenteriae, Shigella flexneri, Shigella sonnei, Enterobacter cloacae, Enterobacter aerogenes, Klebsiella pneumoniae, Klebsiella oxytoca, Serratia marcescens, Francisella tularensis, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia alcalifaciens, Providencia rettgeri, Providencia stuartii, Acinetobacter baumannii, Acinetobacter calcoaceticus, Acinetobacter haemolyticus, Yersinia enterocolitica, Yersinia pestis, Yersinia pseudotuberculosis, Yersinia intermedia, Bordetella pertussis, Bordetella parapertussis, Bordetella bronchiseptica, Haemophilus influenzae, Haemophilus parainfluenzae, Haemophilus haemolyticus, Haemophilus parahaemolyticus, Haemophilus ducreyi, Pasteurella multocida, Pasteurella haemolytica, Branhamella catarrhalis, Helicobacter pylori, Campylobacter fetus, Campylobacter jejuni, Campylobacter coli, Borrelia burgdorferi, Vibrio cholerae, Vibrio parahaemolyticus, Legionella pneumophila, Listeria monocytogenes, Neisseria gonorrhoeae, Neisseria meningitidis, Kingella, Moraxella, Gardnerella vaginalis, Bacteroides fragilis, Bacteroides distasonis, Bacteroides 3452A homology group, Bacteroides vulgatus, Bacteroides ovalus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides eggerthii, Bacteroides splanchnicus, Clostridium difficile, Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium leprae, Corynebacterium diphtheriae, Corynebacterium ulcerans, Streptococcus pneumoniae, Streptococcus agalactiae, Streptococcus pyogenes, Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Staphylococcus intermedius, Staphylococcus hyicus subsp. hyicus, Staphylococcus haemolyticus, Staphylococcus hominis, or Staphylococcus saccharolyticus. In one aspect, the present disclosure relates to methods of treating one or more autoimmune diseases or disorders. In embodiments, the treatment of an autoimmune disease or disorder may involve modulating the immune system with the present Trim7 inhibitors to favor immune inhibition over immune stimulation. Illustrative autoimmune diseases or disorders treatable with the present Trim? inhibitors include those in which the body's own antigens become targets for an immune response, such as, for example, rheumatoid arthritis, systemic lupus erythematosus, diabetes mellitus, ankylosing spondylitis, Sjogren's syndrome, inflammatory bowel diseases (e.g. colitis ulcerosa, Crohn's disease), multiple sclerosis, sarcoidosis, psoriasis, Grave's disease, Hashimoto's thyroiditis, psoriasis, hypersensitivity reactions (e.g., allergies, hay fever, asthma, and acute edema cause Type I hypersensitivity reactions), and vasculitis. Methods of Determining a Cancer Treatment for a Patient; Methods of Selecting a Patient for a Cancer Treatment; and Methods of Treatment In one aspect, the present disclosure relates to a method of determining a cancer treatment for a patient, the method comprising: (a) obtaining a biological sample from a subject; (b) evaluating the biological sample for the expression of Trim?; and ic) selecting the cancer therapy comprising the pharmaceutical composition of any embodiments disclosed herein, if the Trim? is upregulated compared to a compared to a healthy tissue, a prior biological sample obtained from the subject, or another biological sample from patient that is known to be sensitive to an anti-checkpoint agent; and (d) optionally selecting a second cancer therapy comprising an anti-checkpoint agent. In embodiments, the anti-checkpoint agent is selected from an anti-PD-1, anti-PD-LI, anti-PD-L2, and / or anti-CTLA agent. In embodiments, the anticheckpoint agent is selected from an anti-PD-1, anti-PD-L1, anti-PD-L2, and / or anti-CTLA antibody. In one aspect, the present disclosure relates to a method for selecting a patient for a cancer treatment, the method comprising: (a) obtaining a biological sample from a subject; (b) evaluating the biological sample for the expression of Trim?; and ic) selecting the cancer therapy comprising the pharmaceutical composition of any embodiments disclosed herein, if the Trim? is upregulated compared to a compared to a healthy tissue, a prior biological sample obtained from the subject, or another biological sample from patient that is known to be sensitive to an anti-checkpoint agent; and (d) optionally selecting a second cancer therapy comprising an anti-checkpoint agent. In embodiments, the anti-checkpoint agent is selected from an anti-PD-1, anti-PD-LI, anti-PD-L2, and / or anti-CTLA agent. In embodiments, the anticheckpoint agent is selected from an anti-PD-1, anti-PD-L1, anti-PD-L2, and / or anti-CTLA antibody. In one aspect, the present disclosure relates to a method of treating cancer, the method comprising: (a) obtaining a biological sample from a subject; (b) evaluating the biological sample for the expression of Trim?; and (c) administering the cancer therapy comprising the pharmaceutical composition of any embodiments disclosed herein, if the Trim? is upregulated compared to a compared to a healthy tissue, a prior biological sample obtained from the subject, or another biological sample from patient that is known to be sensitive to an anti-checkpoint agent; and (d) optionally administering a second cancer therapy comprising an anti-checkpoint agent. In embodiments, the anti-checkpoint agent is selected from an anti-PD-1, anti-PD-LI, anti-PD-L2, and / or anti-CTLA agent. In embodiments, the anti-checkpoint agent is selected from an anti-PD-1, anti-PD-L1, anti-PD-L2, and / or anti-CTLA antibody. In embodiments, the biological sample is a fresh tissue sample, frozen tumor tissue specimen, cultured cells, circulating tumor cells, or a formalin-fixed paraffin-embedded tumor tissue specimen. In embodiments, the biological sample is a biopsy sample, optionally wherein the biopsy sample is selected from endoscopic biopsy, bone marrow biopsy, endoscopic biopsy (e.g., cystoscopy, bronchoscopy and colonoscopy), needle biopsy (e.g., fine-needle aspiration, core needle biopsy, vacuum-assisted biopsy, X-ray-assisted biopsy, computerized tomography (CT)-assisted biopsy, magnetic resonance imaging (MRI)-assisted biopsy and ultrasound-assisted biopsy), skin biopsy (e.g., shave biopsy, punch biopsy, and incisional biopsy) and surgical biopsy. In embodiments, the biological sample comprises a body fluid selected from blood, plasma, serum, lacrimal fluid, tears, bone marrow, blood, blood cells, ascites, tissue or fine needle biopsy sample, cell-containing body fluid, free floating nucleic acids, sputum, saliva, urine, cerebrospinal fluid, peritoneal fluid, pleural fluid, feces, lymph, gynecological fluid, skin swab, vaginal swab, oral swab, nasal swab, washing or lavage such as a ductal lavage or broncheoalveolar lavage, aspirate, scraping, bone marrow specimen, tissue biopsy specimen, surgical specimen, feces, other body fluids, secretions, and / or excretions, and / or cells therefrom. In embodiments, the biological sample comprises at least one tumor cell. In embodiments, the evaluating is performed by DNA sequencing, RNA sequencing, immunohistochemical staining, western blotting, in cell western, immunofluorescent staining, ELISA, and fluorescent activating cell sorting (FACS) or a combination thereof. In embodiments, the evaluating is performed by contacting the sample with an agent that specifically binds to Trim7. In embodiments, the agent that specifically binds to one or proteins comprises an antibody, antibody-like molecule or binding a fragment thereof. In embodiments, the evaluating is performed by contacting the sample with an agent that specifically binds to one or more of nucleic acids of Trim7. In embodiments, the agent that specifically binds to one or more of the nucleic acids is a nucleic acid primer or probe. Combination Therapies and Conjugation In embodiments, the disclosure provides for Trim7 inhibitors and methods that further comprise administering an additional agent to a subject. In embodiments, the disclosure pertains to co-administration and / or co-formulation. Any of the compositions described herein may be co-formulated and / or co-administered. In embodiments, any Trim7 inhibitor described herein acts synergistically when co-administered with another agent and is administered at doses that are lower than the doses commonly employed when such agents are used as monotherapy. In embodiments, inclusive of, without limitation, cancer applications, the present disclosure pertains to chemotherapeutic agents as additional agents. Examples of chemotherapeutic agents include, but are not limited to, alkylating agents such as thiotepa and CYTOXAN cyclosphosphamide; alkyl sulfonates such as busulfan, improsulfan and piposulfan; aziridines such as benzodopa, carboquone, meturedopa, and uredopa; ethylenimines and methylamelamines including altretamine, triethylenemelamine, trietylenephosphoramide, triethiylenethiophosphoramide and trimethylolomelamine; acetogenins (e.g, bullatacin and bullatacinone); a camptothecin (including the synthetic analogue topotecan); bryostatin; cally statin; CC-1065 (including its adozelesin, carzelesin and bizelesin synthetic analogues); cryptophycins (e.g., cryptophycin 1 and cryptophycin 8); dolastatin; duocarmycin (including the synthetic analogues, KW-2189 and CB 1 -TM1); eleutherobin; pancratistatin; a sarcodictyin; spongistatin; nitrogen mustards such as chlorambucil, chlornaphazine, cholophosphamide, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novembichin, phenesterine, prednimustine, trofosfamide, uracil mustard; nitrosureas such as carmustine, chlorozotocin, fotemustine, lomustine, nimustine, and ranimnustine; antibiotics such as the enediyne antibiotics (e.g., calicheamicin, especially calicheamicin gammall and calicheamicin omegall (see, e.g., Agnew, Chern. Inti. Ed. Engl., 33: 183-186 (1994)); dynemicin, including dynemicin A; bisphosphonates, such as clodronate; an esperamicin; as well as neocarzinostatin chromophore and related chromoprotein enediyne antibiotic chromophores), aclacinomysins, actinomycin, authramycin, azaserine, bleomycins, cactinomycin, carabicin, caminomycin, carzinophilin, chromomycinis, dactinomycin, daunorubicin, detorubicin, 6-diazo-5-oxo-L-norleucine, ADRIAMYCIN doxorubicin (including morpholino- doxorubicin, cyanomorpholino-doxorubicin, 2-pyrrolino-doxorubicin and deoxy doxorubicin), epirubicin, esorubicin, idarubicin, marcellomycin, mitomycins such as mitomycin C, mycophenolic acid, nogalamycin, olivomycins, peplomycin, potfiromycin, puromycin, quelamycin, rodorubicin, streptonigrin, streptozocin, tubercidin, ubenimex, zinostatin, zorubicin; anti-metabolites such as methotrexate and 5-fluorouracil (5-FU); folic acid analogues such as denopterin, methotrexate, pteropterin, trimetrexate; purine analogs such as fludarabine, 6-mercaptopurine, thiamiprine, thioguanine; pyrimidine analogs such as ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocitabine, floxuridine; androgens such as calusterone, dromostanolone propionate, epitiostanol, mepitiostane, testolactone; anti-adrenals such as minoglutethimide, mitotane, trilostane; folic acid replenisher such as frolinic acid; aceglatone; aldophosphamide glycoside; aminolevulinic acid; eniluracil; amsacrine; bestrabucil; bisantrene; edatraxate; demecolcine; diaziquone; elformithine; elliptinium acetate; an epothilone; etoglucid; gallium nitrate; hydroxyurea; lentinan; lonidainine; maytansinoids such as maytansine and ansamitocins; mitoguazone; mitoxantrone; mopidanmol; nitraerine; pentostatin; phenamet; pirarubicin; losoxantrone; podophyllinic acid; 2-ethylhydrazide; procarbazine; PSK polysaccharide complex (JHS Natural Products, Eugene, Oreg.); razoxane; rhizoxin; sizofuran; spirogermanium; tenuazonic acid; triaziquone; 2,2',2"-trichlorotriethylamine; trichothecenes (e.g., T-2 toxin, verracurin A, roridin A and anguidine); urethan; vindesine; dacarbazine; mannomustine; mitobronitol; mitolactol; pipobroman; gacytosine; arabinoside ("Ara-C"); cyclophosphamide; thiotepa; taxoids, e.g., TAXOL paclitaxel (Bristol-Myers Squibb Oncology, Princeton, N.J.), ABRAXANE Cremophor-free, albumin-engineered nanoparticle formulation of paclitaxel (American Pharmaceutical Partners, Schaumberg, 111.), and TAXOTERE doxetaxel (Rhone-Poulenc Rorer, Antony, France); chloranbucil; GEMZAR gemcitabine; 6-thioguanine; mercaptopurine; methotrexate; platinum analogs such as cisplatin, oxaliplatin and carboplatin; vinblastine; platinum; etoposide (VP-16); ifosfamide; mitoxantrone; vincristine; NAVELBINE, vinorelbine; novantrone; teniposide; edatrexate; daunomycin; aminopterin; xeloda; ibandronate; irinotecan (Camptosar, CPT-11) (including the treatment regimen of irinotecan with 5-FU and leucovorin); topoisomerase inhibitor RFS 2000; difluoromethylornithine (DMFO); retinoids such as retinoic acid; capecitabine; combretastatin; leucovorin (LV); oxaliplatin, including the oxaliplatin treatment regimen (FOLFOX); lapatinib (TYKERB); inhibitors of PKC-a, Raf, H-Ras, EGFR (e.g., erlotinib (Tarceva)) and VEGF-A that reduce cell proliferation and pharmaceutically acceptable salts, acids or derivatives of any of the above. In addition, the methods of treatment can further include the use of radiation. In addition, the methods of treatment can further include the use of photodynamic therapy. In embodiments, inclusive of, without limitation, cancer applications, the present additional agent is one or more immune-modulating agents selected from an agent that blocks, reduces and / or inhibits PD-1 and PD-L1 or PD-L2 and / or the binding of PD-1 with PD-L1 or PD-L2 (by way of non-limiting example, one or more of nivolumab (ONO-4538 / BMS-936558, MDX1106, OPDIVO, BRISTOL MYERS SQUIBB), pembrolizumab (KEYTRUDA, Merck), MK-3475 (MERCK), BMS 936559 (BRISTOL MYERS SQUIBB), atezolizumab (TECENTRIQ, GENENTECH), MPDL328OA (ROCHE)), an agent that increases and / or stimulates CD137 (4-1BB) and / or the binding of CD137 (4-1BB) with one or more of 4-1BB ligand (by way of non-limiting example, urelumab (BMS-663513 and anti-4-1 BB antibody), and an agent that blocks, reduces and / or inhibits the activity of CTLA-4 and / or the binding of CTLA-4 with one or more of AP2M1, CD80, CD86, SHP-2, and PPP2R5A and / or the binding of 0X40 with OX40L (by way of nonlimiting example GBR 830 (GLENMARK), MEDI6469 (MEDIMMUNE). In embodiments, inclusive of, without limitation, infectious disease applications, the present disclosure pertains to anti-infectives as additional agents. In embodiments, the anti-infective is an anti-viral agent including, but not limited to, Abacavir, Acyclovir, Adefovir, Amprenavir, Atazanavir, Cidofovir, Darunavir, Delavirdine, Didanosine, Docosanol, Efavirenz, Elvitegravir, Emtricitabine, Enfuvirtide, Etravirine, Famciclovir, and Foscarnet. In embodiments, the anti-infective is an anti-bacterial agent including, but not limited to, cephalosporin antibiotics (cephalexin, cefuroxime, cefadroxil, cefazolin, cephalothin, cefaclor, cefamandole, cefoxitin, cefprozil, and ceftobiprole); fluoroquinolone antibiotics (cipro, Levaquin, floxin, tequin, avelox, and norflox); tetracycline antibiotics (tetracycline, minocycline, oxytetracycline, and doxycycline); penicillin antibiotics (amoxicillin, ampicillin, penicillin V, dicloxacillin, carbenicillin, vancomycin, and methicillin); monobactam antibiotics (aztreonam); and carbapenem antibiotics (ertapenem, doripenem, imipenem / cilastatin, and meropenem). In embodiments, the anti-infectives include anti-malarial agents (e.g., chloroquine, quinine, mefloquine, primaquine, doxycycline, artemether / lumefantrine, atovaquone / proguanil and sulfadoxine / pyrimethamine), metronidazole, tinidazole, ivermectin, pyrantel pamoate, and albendazole. In embodiments, inclusive, without limitation, of autoimmune applications, the additional agent is an immunosuppressive agent. In embodiments, the immunosuppressive agent is an anti-inflammatory agent such as a steroidal anti-inflammatory agent or a non-steroidal anti-inflammatory agent (NSAID). Steroids, particularly the adrenal corticosteroids and their synthetic analogues, are well known in the art. Examples of corticosteroids useful in the present disclosure include, without limitation, hydroxyltriamcinolone, alpha-methyl dexamethasone, beta-methyl betamethasone, beclomethasone dipropionate, betamethasone benzoate, betamethasone dipropionate, betamethasone valerate, clobetasol valerate, desonide, desoxymethasone, dexamethasone, diflorasone diacetate, diflucortolone valerate, fluadrenolone, fluclorolone acetonide, flumethasone pivalate, fluosinolone acetonide, fluocinonide, flucortine butylester, fluocortolone, fluprednidene (fluprednylidene) acetate, flurandrenolone, halcinonide, hydrocortisone acetate, hydrocortisone butyrate, methylprednisolone, triamcinolone acetonide, cortisone, cortodoxone, flucetonide, fludrocortisone, difluorosone diacetate, fluradrenolone acetonide, medrysone, amcinafel, amcinafide, betamethasone and the balance of its esters, chloroprednisone, clocortelone, clescinolone, dichlorisone, difluprednate, flucloronide, flunisolide, fluoromethalone, fluperolone, fluprednisolone, hydrocortisone, meprednisone, paramethasone, prednisolone, prednisone, beclomethasone dipropionate. (NSAIDS) that may be used in the present disclosure, include but are not limited to, salicylic acid, acetyl salicylic acid, methyl salicylate, glycol salicylate, salicylmides, benzyl-2,5-diacetoxybenzoic acid, ibuprofen, fulindac, naproxen, ketoprofen, etofenamate, phenylbutazone, and indomethacin. In embodiments, the immunosupressive agent may be cytostatics such as alkylating agents, antimetabolites (e.g, azathioprine, methotrexate), cytotoxic antibiotics, antibodies (e.g, basiliximab, daclizumab, and muromonab), anti-immunophilins (e.g, cyclosporine, tacrolimus, sirolimus), inteferons, opioids, TNF binding proteins, my cophenolates, and small biological agents (e.g, fingolimod, myriocin). In embodiments, inclusive, without limitation, the additional agent is a kras inhibitor (e.g. a kras G12C inhibitor). In embodiments, the kras inhibitor is selected from BI2865, MRTX113, sotorasib (AMG510), and adagrasib (MRTX849). In embodiments, inclusive, without limitation, the additional agent is a braf inhibitor. In embodiments, the braf inhibitor is selected from vemurafenib, dabrafenib and encorafenib. In embodiments, inclusive, without limitation, the additional agent is a MEK inhibitor. In embodiments, the MEK inhibitor is selected from binimetinib (MEK162), cobimetinib (XL518), selumetinib, and trametinib (GSK1120212). In embodiments, the Trim? inhibitors (and / or additional agents) described herein, include derivatives that are modified, i.e., by the covalent attachment of any type of molecule to the composition such that covalent attachment does not prevent the activity of the composition. For example, but not by way of limitation, derivatives include composition that have been modified by, inter alia, glycosylation, lipidation, acetylation, pegylation, phosphorylation, amidation, derivatization by known protecting / blocking groups, proteolytic cleavage, linkage to a cellular ligand or other protein, etc. Any of numerous chemical modifications can be carried out by known techniques, including, but not limited to specific chemical cleavage, acetylation, formylation, metabolic synthesis of turicamycin, etc. Additionally, the derivative can contain one or more non-classical amino acids. In still other embodiments, the Trim7 inhibitors (and / or additional agents) described herein further comprise a cytotoxic agent, comprising, in illustrative embodiments, a toxin, a chemotherapeutic agent, a radioisotope, and an agent that causes apoptosis or cell death. Such agents may be conjugated to a composition described herein. The Trim7 inhibitors (and / or additional agents) described herein may thus be modified post-translationally to add effector moieties such as chemical linkers, detectable moieties such as for example fluorescent dyes, enzymes, substrates, bioluminescent materials, radioactive materials, and chemiluminescent moieties, or functional moieties such as for example streptavidin, avidin, biotin, a cytotoxin, a cytotoxic agent, and radioactive materials. Subjects and / or Animals In embodiments, the subject and / or animal is a mammal, e.g., a human, mouse, rat, guinea pig, dog, cat, horse, cow, pig, rabbit, sheep, or non-human primate, such as a monkey, chimpanzee, or baboon. In embodiments, the subject and / or animal is a non-mammal, such, for example, a zebrafish. In embodiments, the subject and / or animal may comprise fluorescently-tagged cells (with e.g. GFP). In embodiments, the subject and / or animal is a transgenic animal comprising a fluorescent cell. In embodiments, the subject and / or animal is a human. In embodiments, the human is a pediatric human. In embodiments, the human is an adult human. In embodiments, the human is a geriatric human. In embodiments, the human may be referred to as a patient. In certain embodiments, the human has an age in a range of from about 0 months to about 6 months old, from about 6 to about 12 months old, from about 6 to about 18 months old, from about 18 to about 36 months old, from about 1 to about 5 years old, from about 5 to about 10 years old, from about 10 to about 15 years old, from about 15 to about 20 years old, from about 20 to about 25 years old, from about 25 to about 30 years old, from about 30 to about 35 years old, from about 35 to about 40 years old, from about 40 to about 45 years old, from about 45 to about 50 years old, from about 50 to about 55 years old, from about 55 to about 60 years old, from about 60 to about 65 years old, from about 65 to about 70 years old, from about 70 to about 75 years old, from about 75 to about 80 years old, from about 80 to about 85 years old, from about 85 to about 90 years old, from about 90 to about 95 years old or from about 95 to about 100 years old. In embodiments, the subject is a non-human animal, and therefore the disclosure pertains to veterinary use. In a specific embodiment, the non-human animal is a household pet. In another specific embodiment, the non-human animal is a livestock animal. Kits The disclosure provides kits that can simplify the administration of any agent described herein. An illustrative kit of the disclosure comprises any composition described herein in unit dosage form. In one embodiment, the unit dosage form is a container, such as a pre-filled syringe, which can be sterile, containing any agent described herein and a pharmaceutically acceptable carrier, diluent, excipient, or vehicle. The kit can further comprise a label or printed instructions instructing the use of any agent described herein. The kit may also include a lid speculum, topical anesthetic, and a cleaning agent for the administration location. The kit can also further comprise one or more additional agent described herein. In one embodiment, the kit comprises a container containing an effective amount of a composition of the disclosure and an effective amount of another composition, such those described herein. Any aspect or embodiment described herein can be combined with any other aspect or embodiment as disclosed herein The disclosure will be further described in the following examples, which do not limit the scope of the disclosure described in the claims. EXAMPLES The examples herein are provided to illustrate advantages and benefits of the present disclosure and to further assist a person of ordinary skill in the art with preparing or using the Trim7 inhibitors of the present disclosure. The examples herein are also presented in order to more fully illustrate the preferred aspects of the present disclosure. The examples should in no way be construed as limiting the scope of the present disclosure, as defined by the appended claims. The examples can include or incorporate any of the variations, aspects or embodiments of the present disclosure described above. The variations, aspects or embodiments described above may also further each include or incorporate the variations of any or all other variations, aspects or embodiments of the present disclosure. Example 1: Synthesis of compound of the disclosure Synthesis of (fert-butoxycarbonyl)-L-leucyl-L-phenylalanine (lnt-1): lnt-1 a Preparation of methyl (tert-butoxycarbonyl)-L-leucyl-L-phenylalaninate (lnt-1 a): To a solution of (2S)-2-{[(terf-butoxy)carbonyl]amino}-4-methylpentanoic acid (2.0 g, 8.7 mmol, 1.0 eq.) in DCM (40 mL) was added methyl (2S)-2-amino-3-phenylpropanoate HCI (2.2 g, 10.4 mmol, 1.2 eq.), HATU (4.3 g, 11.2 mmol, 1.3 eq.), and then triethylamine (3.6 mL, 25.9 mmol, 3.0 eq.). The reaction was stirred at room temperature for 12 h under nitrogen atmosphere. After completion, the reaction was quenched with water (50 mL). The two layers were separated, and the aqueous layer was extracted with DCM (20 mL x 3). The combined organic layer was then washed with sat. NaCI solution (50 mL), dried with Na2SO4, filtered, and concentrated. The residue was purified by silica gel column chromatography using hexane / ethyl acetate as the gradient to afford the title compound as a white solid (2.82 g, 83% yield). LCMS ESI-MS m / z: = 393 [M+H]+. Preparation of (tert-butoxycarbonyl)-L-leucyl-L-phenylalanine (lnt-1): To a solution of methyl (tert-butoxycarbonyl)-L-leucyl-L-phenylalaninate (lnt-1a) (558.0 mg, 1.4 mmol, 1.0 eq.) in THF (10 mL) was added 1 M NaOH (3.6 mL, 3.55 mmol, 2.5 eq.). The reaction was stirred at room temperature for 12 h. After completion, the reaction was concentrated and acidify with 1 N HCI. The residue was extracted with DCM (10 mL x 3). The combined organic layer was washed with water (15 mL), sat. NaCI solution (15 mL), dried with Na2SO4, filter, and concentrated to afford the title compound without purification as a white solid (531 mg, 98% yield). LCMS ESI-MS m / z: = 379 [M+H]+. 1H NMR (400 MHz, CHLOROFORM-d) 5 = 7.31 - 7.14 (m, 5H), 6.84 (br s, 1H), 4.95 (br s, 1H), 4.82 (br s, 1H), 4.18 (br s, 1H), 3.18 (br d, J = 10.0 Hz, 1H), 3.01 (br dd, J = 6.1, 14.1 Hz, 1H), 1.55 -1.50 (m, 1H), 1.45 (br s, 9H), 0.90 (brd, 0 = 5.6 Hz, 6H). Synthesis of tert-butyl L-phenylalanyl-L-glutaminate (lnt-2): lnt-2a lnt-2 Preparation of tert-butyl (((9H-fluoren-9-yl)methoxy)carbonyl)-L-phenylalanyl-L-glutaminate (lnt-2a): To a solution of (((9H-fluoren-9-yl)methoxy)carbonyl)-L-phenylalanine (1.7 g, 4.4 mmol, 1.05 eq.) in DMF (14 mL) was added tert-butyl (S)-2-amino-4-carbamoylbutyrate HCI (1.0 g, 4.2 mmol, 1.0 eq.), HATU (1.7 g, 4.6 mmol, 1.1 eq.), and then triethylamine (1.3 mL, 9.2 mmol, 2.2 eq.). The reaction was stirred at room temperature under nitrogen atmosphere for 12 h. Precipitation formed after 15 min. The solid was filtered and washed with ethyl acetate (50 mL) to afford the title compound without further purification as a white solid (2.6 g, 100% yield). lnt-2 Preparation of tert-butyl L-phenylalanyl-L-glutaminate (lnt-2): To a cooled solution of fert-butyl (((9H-fluoren-9-yl)methoxy)carbonyl)-L-phenylalanyl-L-glutaminate (lnt-2a) (2.6 g, 4.6 mmol, 1.0 eq.) in THF (30 mL) atO °C was added 1-dodecanethiol (1.2 mL, 5 mmol, 1.1 eq.), followed by DBU (0.68 mL, 4.5 mmol, 1.0 eq.) The reaction was stirred from 0 °C to room temperature for 4 h. After completion, the reaction was concentrated and was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a white solid (1.1 g, 71% yield). LCMS ESI-MS m / z: = 350 [M+H]+. 1H NMR (400 MHz, DMSO-d6) 5 = 8.19 (brd, J= 7.8 Hz, 1H), 7.31 -7.18 (m, 5H), 6.79 (br s, 1H), 4.14 (br d, J = 5.4 Hz, 1H), 3.48 - 3.38 (m, 1H), 2.98 (dd, J = 4.3, 13.4 Hz, 1H), 2.65 - 2.53 (m, 1H), 2.17-2.03 (m, 2H), 1.92 (brd, J= 8.0 Hz, 2H), 1.41 (s, 9H). Preparation of tert-butyl (tert-butoxycarbonyl)-L-leucyl-L-phenylalanyl-L-glutaminate (1a): To a solution of (S)-2-{(S)-2-[(fert-butyl)(oxycarbonylamino)]-4-methylvalerylamino}-3-phenylpropionic acid (lnt-1) (200 mg, 0.53 mmol, 1.0 eq.) in DMF (2.6 mL) was added tert-butyl (S)-2-amino-4-carbamoy I butyrate (139 mg, 0.58 mmol, 1.1 eq.), HATU (241 mg, 0.63 mmol, 1.2 eq.), and then triethylamine (0.18 mL, 1.32 mmol, 2.5 eq.). The reaction was stirred at room temperature at nitrogen atmosphere. After the completion, the reaction was quenched with water (10 mL) and extracted with ethyl acetate (5 mL x 3). The combined organic layer was washed with sat. NaCI solution (10 mL), dried with Na2SO4, filter, and concentrated. The residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound a white solid (238 mg, 80% yield). LCMS ESI-MS m / z: = 563 [M+H]+. Preparation of L-leucyl-L-phenylalanyl-L-glutamine (1b): To a solution fert-butyl (ferf-butoxycarbonyl)-L-leucyl-L-phenylalanyl-L-glutaminate (1a) (80 mg, 0.14 mmol, 1.0 eq.) in DCM (0.7 mL) was added TFA (0.3 mL) to make a 30% TFA / DCM solution. The reaction was stirred at room temperature for 12 h. After completion, the reaction was concentrated to afford the title compound as an oil (90 mg, 99% yield). LCMS ESI-MS m / z: = 407 [M+H]+. SMI-1 Preparation of acryloyl-L-leucyl-L-phenylalanyl-L-glutamine (SMI-1): To a cooled solution of L-leucyl-L-phenylalanyl-L-glutamine (1b) (90 mg, 0.14 mmol, 1.0 eq.) in 1N NaOH (1 mL) at 0 °C was added acrylyl chloride (92 pL, 1.1 mmol, 8.0 eq.) dropwise. After a few minutes, white precipitate formed. After completion, the white solid was filtered and washed with water. The solid was dissolved in DMSO for Prep HPLC purification using water / MeCN + 0.1% formic acid gradient to afford the title compound as a white solid (26 mg, 40% yield). LCMS ESI-MS m / z: = 461 [M+H]+. 1H NMR (400 MHz, METHANOL-d4) 5 = 8.22-8.10 (m, 1H), 8.06-7.97 (m, 1H), 7.18-7.03 (m, 5H), 6.25 - 6.06 (m, 2H), 5.62 - 5.49 (m, 1H), 4.54 - 4.43 (m, 1H), 4.35 - 4.23 (m, 2H), 3.17 - 3.06 (m, 1H), 2.93 - 2.81 (m, 1H), 2.24 - 2.04 (m, 3H), 1.91 - 1.76 (m, 1H), 1.52-1.41 (m, 1H), 1.40 -1.34 (m, 2H), 0.85 - 0.79 (m, 3H), 0.79 -0.73 (m, 3H). Preparation of propionyl-L-leucyl-L-phenylalanyl-L-glutamine (SMI-4): To a cooled solution of L-leucyl-L-phenylalanyl-L-glutamine (1b) (102 mg, 0.2 mmol, 1.0 eq.) in DCM (1.3 mL) at 0 °C was added DIPEA (171 pL, 0.98 mmol, 1.5 eq.), and then propionyl propionate (38 pL, 0.29 mmol, 1.5 eq.). The reaction was stirred at 0 °C to room temperature for 3 h. The reaction was concentrated and purified by reverse phase chromatography using water / MeCN + 0.1% formic acid as the gradient to afford the title compound as a white solid (24 mg, 26% yield). LCMS ESI-MS m / z: = 463 [M+H]+. 1H NMR (400 MHz, METHANOL-d4) 5 = 7.33-7.18 (m, 5H), 4.70 - 4.56 (m, 1H), 4.43 (dd, J = 3.8, 9.3 Hz, 1H), 4.31 (t, J = 7.5 Hz, 1H), 3.46 - 3.35 (m, 1H), 3.22 (dd, J = 5.3, 14.1 Hz, 1H), 2.99 (dd, J= 9.0,14.0Hz, 1H), 2.35-2.16 (m, 4H), 2.08- 1.90 (m, 1H), 1.67-1.52 (m, 1H), 1.50-1.40 (m, 2H), 1.11 (t, J = 7.6 Hz, 3H), 0.97-0.85 (m, 6H). DIPEA. DCM 0 °C Preparation of acetyl-L-leucyl-L-phenylalanyl-L-glutamine (SMI-5): SMI-5 was synthesized by using L-leucyl-L- 5 phenylalanyl-L-glutamine (1b) (100 mg, 0.19 mmol, 1.0 eq.) and acetyl acetate (27 piL, 0.29 mmol, 1.5 eq.) by following the procedure from SMI-4. The reaction was concentrated and purified by reverse phase chromatography using water / MeCN + 0.1% formic acid as the gradient to afford the title compound as a white solid (29 mg, 33% yield). LCMS ESI-MS m / z: = 449 [M+H]+. 1H NMR (400 MHz, METHANOL-d4) 5 = 7.20 - 7.07 (m, 5H), 4.53 - 4.46 (m, 1H), 4.37-4.24 (m, 1H), 4.18 (t, J = 7.6 Hz, 1H), 3.11 (dd, J = 5.2,14.1 Hz, 1H), 2.86 (dd, J= 9.3, 14.0 Hz, 1H), 10    2.23-2.15 (m, 2H), 2.14-2.05 (m, 1H), 1.91 - 1.79 (m, 4H), 1.51 -1.40 (m, 1H), 1.35- 1.29 (m, 2H), 0.84-0.73 (m, 6H). 4a Preparation of tert-butyl L-leucyl-L-phenylalanyl-L-glutarninate (4a): To solution of tert-butyl (ferf-butoxycarbonyl)- 15 L-leucyl-L-phenylalanyl-L-glutaminate (1a) (80 mg, 0.14 mmol, 1.0 eq.) in tBuOAc:DCM (0.71 mL, 4:1) was added methanesulfonic acid (18 piL, 0.28 mmol, 2.0 eq.). The reaction was stirred at room temperature for 16 h. After completion, the reaction was quenched with triethylamine (99 piL, 0.71 mmol, 5.0 eq.) and stirred for 5 min. It was diluted with MeOH and concentrated down for silica gel purification using DCM / MeOH +1% NH4OH as the gradient to afford the title compound as an oil (58 mg, 89% yield). LCMS ESI-MS m / z: = 463 [M+H]+. Preparation of tert-butyl but-2-ynoyl-L-leucyl-L-phenylalanyl-L-glutaminate (4b): Compound 4b was synthesized 5 using tert-butyl L-leucyl-L-phenylalanyl-L-glutaminate (4a) (58 mg, 0.12 mmol, 1.0 eq.) and 2-butynoic acid (12 mg, 0.14 mmol, 1.1 eq.) by following the procedure from Compound 1a. The crude residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a white solid (53 mg, 79% yield.) LCMS ESI-MS m / z: = 529 [M+H]+. 10 Preparation of but-2-ynoyl-L-leucyl-L-phenylalanyl-L-glutamine (SMI-24): SMI-24 was synthesized using tert-butyl but-2-ynoyl-L-leucyl-L-phenylalanyl-L-glutaminate (4b) (53 mg, 0.10 mmol, 1.0 eq) in 50% TFA / DCM for 3 h by following the procedure from Compound 1b. The crude residue was purified by Prep HPLC using water / MeCN + 0.1% formic acid as the gradient to afford the title compound as a white solid (32 mg, 68% yield). LCMS ESI-MS m / z: = 473 [M+H]* 1H NMR (400 MHz, DMSO-d6) 5 = 8.15 (d, J = 7.8 Hz, 1H), 7.83 (t, J= 7.2 Hz, 2H), 7.70 (br d, J = 4.5 15 Hz, 1H), 7.26-7.11 (m, 4H), 4.50 (dt, J= 4.1, 8.7 Hz, 1H), 4.25-4.10 (m, 2H), 3.05 (dd, J = 4.3, 14.1 Hz, 1H), 2.81 (dd, J = 9.5, 14.0 Hz, 1H), 2.55 (d, J = 4.5 Hz, 3H), 2.17 - 2.03 (m, 4H), 2.02 - 1.91 (m, 1H), 1.85 -1.73 (m, 1H), 1.54- 1.42 (m, 1H), 1.37 - 1.29 (m, 2H), 0.95 (t, J = 7.6 Hz, 3H), 0.86 - 0.74 (m, 6H). HATU. Et3N, DCM rt 1 N NaOH THF, rt 0 \ HATU, Et3N DMF, rt Preparation of methyl (S)-2-((S)-2-((tert-butoxycarbonyl)amino)-4-methylpentanamido)-3-(m-tolyl)propanoate (5a): Compound 5a was synthesized using (fert-butoxycarbonyl)-L-leucine (150 mg, 0.65 mmol, 1.1 eq.) and methyl 5 (S)-2-amino-3-(m-tolyl)propanoate (138 mg, 0.71 mmol, 1.1 eq.) by following the procedure from Compound 1a. The crude residue was purified by silica gel chromatography using hexane / ethyl acetate as the gradient to afford the title compound as an oil (224 mg, 84% yield). LCMS ESI-MS m / z: = 407 [M+H]+. Preparation of (S)-2-((S)-2-((tert-butoxycarbonyl)arnino)-4-methylpentanamido)-3-(m-tolyl)propanoic acid (5b): 10 Compound 5b was synthesized using methyl (S)-2-((S)-2-((fert-butoxycarbonyl)amino)-4-methylpentanamido)-3-(m-tolyl)propanoate (5a) (224 mg, 0.55 mmol, 1.0 eq.) by following the procedure from Compound lnt-1 to afford title compound without further purification as a white solid (205 mg, 95% yield). LCMS ESI-MS m / z: = 393 [M+H]+. Preparation of tert-butyl ((S)-2-((S)-2-((tert-butoxycarbonyl)amino)-4-methylpentanamido)-3-(m- 15 tolyl)propanoyl)-L-glutaminate (5c): Compound 5c was synthesized using (S)-2-((S)-2-((tert- butoxycarbonyl)amino)-4-methylpentanamido)-3-(m-tolyl)propanoic acid (5b) (0.2 g, 0.51 mmol, 1.0 eq.) and tertbutyl L-glutaminate (134 mg, 0.56 mmol, 1.1 eq.) by following the procedure from Compound 1a. The crude residue was purified by silica gel chromatography using DCM / MeOH gradient to afford the title compound as a white solid (278 mg, 95% yield). LCMS ESI-MS m / z: = 577 [M+H]+. Preparation of ((S)-2-((S)-2-amino-4-methylpentanamido)-3-(rn-tolyl)propanoyl)-L-glutarnine (5d): Compound 5d was synthesized using ferf-butyl ((S)-2-((S)-2-((fert-butoxycarbonyl)amino)-4-methylpentanamido)-3-(m-tolyl)propanoyl)-L-glutaminate (5c) (278 mg, 0.48 mmol, 1.0 eq.) in 30% TFA / DCM by following the procedure from Compound 1b to afford the title compound as an oil (287 mg, 100% yield). LCMS ESI-MS m / z: = 421 [M+H]+. Preparation of ((S)-2-((S)-2-acrylamido-4-methylpentanamido)-3-(m-tolyl)propanoyl)-L-glutamine (SMI-11): SMI-10 was synthesized using ((S)-2-((S)-2-amino-4-methylpentanamido)-3-(m-tolyl)propanoyl)-L-glutamine (5d) (100 mg, 0.19 mmol, 1.0 eq.) and acrylyl chloride (155 piL, 1.92 mmol, 10.0 eq.) by following the procedure from SMI-1. The crude residue was purified by reverse phase chromatography using water / MeCN +0.1% formic acid as the gradient to afford the title compound as a white solid (35 mg, 38% yield). LCMS ESI-MS m / z: = 475 [M+H]+. 1H NMR (400 MHz, METHANOL-d4) 5 = 8.14 (br dd, J = 7.8, 11.8 Hz, 1H), 7.99 (d, J = 7.6 Hz, 1H), 7.05 - 6.99 (m, 1H), 6.96 - 6.88 (m, 3H), 6.22 - 6.09 (m, 2H), 5.57 (dd, J = 2.5, 9.5 Hz, 1H), 4.50 - 4.40 (m, 1H), 4.35 - 4.23 (m, 2H), 3,13 -3.01 (m, 1H), 2.73 - 2.81 (m, 1H), 2.23 - 2.08 (m, 6H), 1.92 - 1.75 (m, 1H), 1.56 - 1.42 (m, 1H), 1.41-1.28 (m, 2H), 0.82 (d, J = 6.5 Hz, 3H), 0.77 (d, J = 6.4 Hz, 3H). Preparation of ((S)-2-((S)-4-rnethyl-2-propionamidopentanamido)-3-(m-tolyl)propanoyl)-L-glutamine (SMI-10): SMI-10 was synthesized using of ((S)-2-((S)-2-amino-4-methylpentanamido)-3-(m-tolyl)propanoyl)-L-glutamine (5d) (100 mg, 0.18 mmol, 1.0 eq.) and propionyl propionate (36 pL, 0.28 mmol, 1.5 eq.) by following the procedure from SMI-4. The crude residue was purified by reverse phase chromatography using water / MeCN + 0.1 % formic acid as the gradient to afford the title compound as a white solid (4.4 mg, 5% yield). LCMS ESI-MS m / z: = 477 [M+H]+. 1H NMR (400 MHz, METHANOL-d4) 5 = 7.91 - 7.77 (m, 1H), 7.09 - 7.00 (m, 1H), 6.99 - 6.86 (m, 3H), 4.59 - 4.43 (m, 5    1H), 4.35 - 4.23 (m, 1H), 4.22 - 4.05 (m, 1H), 3.11 - 3.01 (m, 1H), 2.91 - 2.75 (m, 1H), 2.24 - 2.02 (m, 8H), 1.92 - 1.78 (m, 1H), 1.53- 1.39 (m, 1H), 1.38 - 1.22 (m, 2H), 0.99 (t, J = 7.6 Hz, 3H), 0.85 - 0.73 (m, 6H). Preparation of methyl (tert-butoxycarbonyl)-L-leucyl-L-phenylalanyl-L-glutaminate (7a): Compound 7a was 10 synthesized using (ferf-butoxycarbonyl)-L-leucyl-L-phenylalanine (lnt-1) (100.0 mg, 0.27 mmol, 1.0 eq.) and L-glutamine methyl ester hydrochloride (52.5 mg, 0.27 mmol, 1.0 eq.) by following the procedure from Compound 1a. The crude residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a white solid (132 mg, 96% yield). LCMS ESI-MS m / z: = 521 [M+H]+. 15 Preparation of methyl L-leucyl-L-phenylalanyl-L-glutaminate (7b): Compound 7b was synthesized using methyl (ferf-butoxycarbonyl)-L-leucyl-L-phenylalanyl-L-glutaminate (7a) (38 mg, 73 pmol, 1.0 eq.) in 30% TFA / DCM by following the procedure from Compound 1b to afford the title compound without further purification as an oil (30.7 mg, 100% yield). LCMS ESI-MS m / z: = 421 [M+H]+. SMI-32 Preparation of methyl acryloyl-L-leucyl-L-phenylalanyl-L-glutaminate (SMI-32): To a cooled solution of methyl L-leucyl-L-phenylalanyl-L-glutaminate (7b) (30.7 mg, 73 pmol, 1.0 eq.) at 0 °C was added triethylamine (40 pL, 0.29 mmol, 4.0 eq.), and then acryloyl chloride (12.6 pL, 0.11 mmol, 1.5 eq.) The crude residue was purified by reverse 5 phase chromatography using water / MeCN +0.1% formic acid as the gradient to afford the title compound as a white solid (8.1 mg, 23% yield). LCMS ESI-MS m / z: = 475 [M+H]+. 1H NMR (400 MHz, METHANOL-d4) 5 = 8.35 (br d, J = 7.9 Hz, 1H), 8.27 (br d, J = 7.1 Hz, 1H), 8.14 (br d, J = 7.5 Hz, 1H), 7.29 - 7.18 (m, 5H), 6.34 - 6.21 (m, 2H), 5.70 (dd, J = 2.6, 9.4 Hz, 1H), 4.59 (dt, J = 5.8, 8.2 Hz, 1H), 4.51 - 4.33 (m, 2H), 3.77 - 3.70 (m, 3H), 3.20 (dd, J = 5.7, 13.9 Hz, 1H), 2.99 (dd, 0 = 8.9,13.9 Hz, 1H), 2.35-2.13 (m, 3H), 2.04-1.88 (m, 1H), 1.63-1.43 (m, 3H), 1.40 10    1.24 (m, 1H), 0.94 (d, J = 6.4 Hz, 3H), 0.89 (d, J = 6.4 Hz, 3H). Et3N, DCM, rt Preparation of tert-butyl N2-(((9H-fluoren-9-yl)methoxy)carbonyl)-N5-methyl-L-glutaminate (8a): Compound 8a was synthesized using N-Fmoc-L-glutamic acid tert-butyl ester (750 mg, 1.67 mmol, 1.0 eq.) and a 2.0 M solution of methylamine (0.84 mL, 1.67 mmol, 1.0 eq.) in methanol by following the procedure from Compound 1a. The crude residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a white solid (734 mg, 100% yield). LCMS ESI-MS m / z: = 439 [M+H]+. I O^NH -X Y'Y 0     1 8b Preparation of tert-butyl N5-methyl-L-glutaminate (8b): Compound 8b was synthesized using tert-butyl N2-(((9H-fluoren-9-yl)methoxy)carbonyl)-N5-methyl-L-glutaminate (8a) (350 mg, 0.80 mmol, 1.0 eq.) by following the procedure from Compound lnt-2 to afford the title compound without further purification (173 mg, 100% yield). LCMS ESI-MS m / z: = 217 [M+H]+. I O^NH 8c Preparation of tert-butyl N2-((tert-butoxycarbonyl)-L-phenylalanyl)-N5-methyl-L-glutaminate (8c): Compound 8c was synthesized using tert-butyl N6-methyl-L-glutaminate (8b) (173 mg, 0.8 mmol, 1.0 eq.) and N-(tert-Butoxycarbonyl)-L-phenylalanine (255 mg, 0.96 mmol, 1.2 eq.) by following the procedure from Compound 1a. The crude residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a white solid (300 mg, 81% yield). LCMS ESI-MS m / z: = 464 [M+H]+. Preparation of tert-butyl N2-(L-phenylalanyl)-N5-methyl-L-glutaminate (8d): Compound 8d was synthesized using tert-butyl N2-((tert-butoxycarbonyl)-L-phenylalanyl)-N5-methyl-L-glutaminate (8c) (301 mg, 0.65 mmol, 1.0 eq.) by following the procedure from Compound 4a. The crude residue was purified by silica gel chromatography using DCM / MeOH +1% NH4OH as the gradient to afford the title compound as a white solid (236 mg, 100% yield). LCMS ESI-MS m / z: = 364 [M+H]+. Preparation of tert-butyl N2-(tert-butoxycarbonyl)-L-leucyl-L-phenylalanyl-N5-methyl-L-glutaminate (8e): Compound 8e was synthesized using fert-butyl N2-(L-phenylalanyl)-N5-methyl-L-glutaminate (8d) (118 mg, 0.33 mmol, 1.0 eq.) and N-(fert-butoxycarbonyl)-L-leucine (87.0 mg, 0.36 mmol, 1.1 eq.) by following the procedure from Compound 1a. The crude residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a white solid (124 mg, 66% yield). LCMS ESI-MS m / z: = 577 [M+H]+. Preparation of N2-L-leucyl-L-phenylalanyl-N5-methyl-L-glutamine (8f): Compound 8f was synthesized using fert-butyl N2-(tert-butoxycarbonyl)-L-leucyl-L-phenylalanyl-N5-methyl-L-glutaminate (8e) (122 mg, 0.21 mmol, 1.0 eq.) in 30% TFA / DCM by following the procedure from Compound 1b to afford the title compound without further purification (113 mg, 100% yield). LCMS ESI-MS m / z: = 421 [M+H]+. Preparation of N2-acryloyl-L-leucyl-L-phenylalanyl-N5-methyl-L-glutamine (SMI-21): SMI-21 was synthesized using N2-L-leucyl-L-phenylalanyl-N5-methyl-L-glutamine (8f) (56.5 mg, 0.11 mmol, 1.0 eq.) and acryloyl chloride (14 pL, 0.12 mmol, 1.1 eq.) by following the procedure from SMI-32. The crude residue was purified by reverse phase chromatography using water / MeCN +1% formic acid as the gradient to afford the title compound as a white solid (24.9 mg, 50% yield). LCMS ESI-MS m / z: = 475 [M+H]+. 1H NMR (400 MHz, METHANOL-d4) 5 = 7.32-7.10 (m, 5H), 4.65-4.55 (m, 1H), 4.40 (dd, J= 4.0, 9.1 Hz, 1H), 4.33 (dd, J = 5.7, 9.4 Hz, 1H), 3.24-3.11 (m, 2H), 2.96 (dd, 7=9.1, 14.0 Hz, 1H), 2.33-2.15 (m, 3H), 1.60- 1.50 (m, 1H), 1.44 (dt, 7 = 5.6, 8.6 Hz, 2H), 0.89 (dd, 7 = 6.5, 19.1 Hz, 6H). MesSnOH DCE, 70 °C Preparation of methyl N2-(tert-butoxycarbonyl)-N5,N5-dimethyl-L-glutaminate (9a): Compound 9a was synthesized using N-boc-L-glutamic acid methyl ester (1.0 g, 3.7 mmol, 1.0 eq.) and dimethylamine (2.04 mL, 4.1 5 mmol, 1.1 eq.) by following the procedure from Compound 1a. The crude residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a colorless oil (1.07 g, 100% yield). LCMS ESI-MS m / z: = 289 [M+H]+. I h2n^Y°^ o 9b Preparation of methyl N5,N5-dimethyl-L-glutaminate (9b): Compound 9b was synthesized using methyl N2-(tert- 10 butoxycarbonyl)-N5,N5-dimethyl-L-glutaminate (9a) (1.07 g, 4.8 mmol, 1.0 eq.) in 30% TFA / DCM by following the procedure from Compound 1b. The residue was purified by silica gel chromatography using DCM / MeOH +1% NH4OH as the gradient to afford the title compound as a colorless oil (813 mg, 90% yield). LCMS ESI-MS m / z: = 189 [M+H]+. Preparation of methyl N2-(tert-butoxycarbonyl)-L-leucyl-L-phenylalanyl-N5,N5-dimethyl-L-glutaminate (9c): Compound 9c was synthesized using methyl N5,N5-dimethyl-L-glutaminate (9b) (70 mg, 0.18 mmol, 1.0 eq.) and (ferf-butoxycarbonyl)-L-leucyl-L-phenylalanine (lnt-1) (35.2 mg, 0.18 mmol, 1.0 eq.) by following the procedure from Compound 1a. The residue was purified by silica gel chromatography using hexane / ethyl acetate as the gradient to afford the title compound as a white solid (77 mg, 76% yield). LCMS ESI-MS m / z: = 549 [M+H]+. I 9d Preparation of N2-(fert-butoxycarbonyl)-L-leucyl-L-phenylalanyl-N5,N5-dimethyl-L-glutamine (9d): To a solution of methyl N2-(ferf-butoxycarbonyl)-L-leucyl-L-phenylalanyl-N5,N5-dimethyl-L-glutaminate (9c) (77 mg, 0.15 mmol, 1.0 eq.) in DCE (1 mL) was added trimethyltin hydroxide (80.5 mg, 0.44 mmol, 3.0 eq.). The reaction was heated to 60 °C for 12 h. After completion, the reaction mixture was concentrated and then diluted with ethyl acetate (10 mL), followed by washing with 1 M HCI (5 mL x 3), water (5 mL), sat. NaCI solution (5 mL), dried with Na2SO4, filtered, and concentrated to afford the title compound without further purification (105 mg, 100% yield). LCMS ESI-MS m / z: = 535 [M+H]+. Preparation of N2-L-leucyl-L-phenylalanyl-N5,N5-dimethyl-L-glutamine (9e): Compound 9e was synthesized using N2-(ferf-butoxycarbonyl)-L-leucyl-L-phenylalanyl-N5,N5-dimethyl-L-glutamine (9d) (19 mg, 0.036 mmol, 1.0 eq.) in 30% TFA / DCM by following the procedure from Compound 1b to afford the title compound without further purification (15.4 mg, 100% yield). LCMS ESI-MS m / z: = 435 [M+H]+. Preparation of N2-acryloyl-L-leucyl-L-phenylalanyl-N5,N5-dimethyl-L-glutamine (SMI-30): Compound 9 was synthesized using N2-L-leucyl-L-phenylalanyl-N5,N6-dimethyl-L-glutamine (9e) (15.4 mg, 37 |jmol, 1.0 eq.) and acryloyl chloride (4.5 pL, 55 pmol, 1.5 eq.) by following the procedure from SMI-32. The crude residue was purified by reverse phase chromatography using water / MeCN + 0.1% formic acid as the gradient to afford the title compound as a white solid (2.1 mg, 12% yield). LCMS ESI-MS m / z: = 489 [M+H]+. ^H NMR (400 MHz, METHANOL-d4) 5 = 7.24 (d, J = 4.4 Hz, 5H), 6.29-6.21 (m, 2H), 5.68 (dd, J = 3.1, 8.9 Hz, 1H), 4.65 - 4.56 (m, 2H), 4.49 - 4.40 (m, 1H), 4.40 -4.30 (m, 1H), 3.24-3.12 (m, 1H), 3.14 (s, 1H), 3.03 (s, 4H), 2.92 (s, 4H), 2.40 (s, 3H), 2.25-2.12 (m, 1H), 2.04 5     1.88 (m, 1H), 1.52 (br d, J = 7.5 Hz, 4H), 0.91 (dd, J = 6.4, 15.6 Hz, 6H). Preparation of tert-butyl ((S)-2-((tert-butoxycarbonyl)amino)-3-(pyridin-4-yl)propanoyl)-L-glutaminate (12a): Compound 12a was synthesized using tert-butyl L-glutaminate HCI (380 mg, 1.6 mmol, 1.0 eq.) and (S)-2-((tert- 10 butoxycarbonyl)amino)-3-(pyridin-4-yl)propanoic acid (481 mg, 1.8 mmol, 1.1 eq.) by following the procedure from Compound 1a. The crude residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a white solid (783 mg, 100% yield). LCMS ESI-MS m / z: = 451 [M+H]+. Preparation of tert-butyl ((S)-2-amino-3-(pyridin-4-yl)propanoyl)-L-glutaminate (12b): Compound 12b was 15 synthesized using tert-butyl ((S)-2-((tert-butoxycarbonyl)amino)-3-(pyridin-4-yl)propanoyl)-L-glutaminate (12a) (150 mg, 0.33 mmol, 1.0 eq.) by following the procedure from Compound 4a to afford the title compound without further purification as an oil (117 mg, 100% yield). LCMS ESI-MS m / z: = 351 [M+H]+. Preparation of tert-butyl ((S)-2-((S)-2-((tert-butoxycarbonyl)amino)-4-methylpentanamido)-3-(pyridin-4-yl)propanoyl)-L-glutaminate (12c): Compound 12c was synthesized using tert-butyl ((S)-2-amino-3-(pyridin-4-yl)propanoyl)-L-glutaminate (12b) (117 mg, 0.33 mmol, 1.0 eq.) and (fert-butoxycarbonyl)-L-leucine (89 mg, 0.37 mmol, 1.1 eq.) by following the procedure from Compound 1a. The crude residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a white solid (50 mg, 27% yield). LCMS ESI-MS m / z: = 564 [M+H]+. Preparation of ((S)-2-((S)-2-amino-4-methylpentanamido)-3-(pyridin-4-yl)propanoyl)-L-glutamine (12d): Compound 12d was synthesized using tert-butyl ((S)-2-((S)-2-((fert-butoxycarbonyl)amino)-4-methylpentanamido)-3-(pyridin-4-yl)propanoyl)-L-glutaminate (12c) (50 mg, 89 pmol, 1.0 eq.) in 50% TFA / DCM by following the procedure from Compound 1b to afford the title compound without further purification as an oil (56 mg, 100% yield). LCMS ESIMS m / z: = 408 [M+H]+. Preparation of ((S)-2-((S)-2-acrylamido-4-methylpentanamido)-3-(pyridin-4-yl)propanoyl)-L-glutamine (SMI-18): SMI-18 was synthesized using ((S)-2-((S)-2-amino-4-methylpentanamido)-3-(pyridin-4-yl)propanoyl)-L-glutamine (12d) (8 mg, 12 pmol, 1.0 eq.) and acrylyl chloride (1.0 pL, 12 pmol, 1.0 eq.) by following the procedure from SMI-32. The crude residue was purified by Prep HPLC using water / MeCN + 0.1 % formic acid as the gradient to afford the title compound as a white solid (3 mg, 24% yield). LCMS ESI-MS m / z: = 462 [M+H]+. 1H NMR (400 MHz, METHANOL-d4) 5 = 8.72 (d, J = 4.3 Hz, 1H), 8.45 - 8.41 (m, 2H), 7.51 (dd, J = 4.4, 8.4 Hz, 1H), 7.45 (d, J = 5.9 Hz, 1H), 6.30-6.15 (m, 2H), 5.69 (dd, J= 3.1, 9.0 Hz, 1H), 4.72-4.71 (m, 1H), 4.45-4.34 (m, 2H), 3.24-3.21 (m, 1H), 3.08 (dd, 9.3,13.9 Hz, 1H), 2.35-2.13 (m, 3H), 2.02-1.90 (m, 1H), 1.60-1.55 (m, 1H), 1.50 (td, 7 = 6.4, 8.5 Hz, 2H), 0.91 (dd, J = 6.4,17.6 Hz, 6H). 12d O Et3N, DCM, 0 °C Preparation of ((S)-2-((S)-4-methyl-2-propionamidopentanamido)-3-(pyridin-4-yl)propanoyl)-L-glutamine (SMI-22): SMI-22 was synthesized using ((S)-2-((S)-2-amino-4-methylpentanamido)-3-(pyridin-4-yl)propanoyl)-L-glutamine (12d) (35 mg, 54 pmol, 1.0 eq.) and propionyl chloride (6.5 pL, 71 pmol, 1.3 eq.) by following the procedure from 5    SMI-32. The crude residue was purified by Prep HPLC using water / MeCN + 0.1% formic acid as the gradient to afford the title compound as a white solid (12 mg, 48% yield). LCMS ESI-MS m / z: = 464 [M+H]+. 1H NMR (400 MHz, METHANOL-d4) 5 = 8.61 (br d, J = 5.5 Hz, 2H), 8.46 - 8.39 (m, 1H), 8.32 (br d, J = 7.9 Hz, 1H), 8.01 (br d, J = 6.9 Hz, 1H), 7.76 (br d, J = 3.9 Hz, 2H), 4.82 - 4.76 (m, 1H), 4.48 - 4.36 (m, 1H), 4.32 - 4.23 (m, 1H), 3.53 - 3.36 (m, 1H), 3.24-3.10 (m, 1H), 2.34-2.29 (m, 2H), 2.26-2.16(m, 3H), 2.01-1.88 (m, 1H), 1.67-1.55(m, 1H), 1.54 10    1.43 (m, 2H), 1.10 (t, J = 7.6 Hz, 3H), 0.91 (dd, J = 6.6, 19.2 Hz, 6H). Preparation of tert-butyl (S)-2-(((S)-1-(((S)-5-amino-1-(fert-butoxy)-1,5-dioxopentan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)carbamoyl)pyrrolidine-1-carboxylate (14a): Compound 14a was synthesized using tert-butyl 15 L-phenylalanyl-L-glutaminate (lnt-2) (66 mg, 0.19 mmol, 1.0 eq.) and ferf-butoxycarbonyl)-L-proline (44 mg, 0.21 mmol, 1.1 eq.) by following the procedure from Compound 1a. The crude residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a white solid (90 mg, 87% yield). LCMS ESI-MS m / z: = 547 [M+H]+. 14b Preparation of L-prolyl-L-phenylalanyl-L-glutamine (14b): Compound 14b was synthesized using fert-butyl (S)-2-(((S)-1-(((S)-5-amino-1-(fert-butoxy)-1,5-dioxopentan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)carbamoyl)pyrrolidine-1-carboxylate (14a) (90 mg, 0.16 mmol, 1.0 eq.) in 30% TFA / DCM by following the procedure from Compound 1b to afford the title compound without further purification as an oil (102 mg, 100% yield). LCMS ESI-MS m / z: = 391 [M+H]+. Preparation of acryloyl-L-prolyl-L-phenylalanyl-L-glutamine (SMI-34): SMI-34 was synthesized using L-prolyl-L-phenylalanyl-L-glutamine (14b) (80 mg, 0.13 mmol, 1.0 eq.) and acrylyl chloride (13 pL, 0.17 mmol, 1.3 eq.) by following the procedure from SMI-32. The crude residue was purified by reverse phase purification using water / MeCN + 0.1% formic acid to afford the title compound as a white solid (17 mg, 29% yield). LCMS ESI-MS m / z: = 445 [M+H]+. 1H NMR (400 MHz, METHANOL-d4) 5 = 7.32-7.17 (m, 5H), 6.61 (dd, J= 10.4, 16.8 Hz, 1H), 6.26 (dd, J = 1.8, 16.8 Hz, 1H), 5.88 - 5.79 (m, 1H), 5.78 - 5.72 (m, 1H), 4.57 (dd, J = 5.3, 9.6 Hz, 1H), 4.45 - 4.35 (m, 2H), 3.73-3.46 (m, 2H), 3.25 (dd, J = 5.4, 14.0 Hz, 1H), 3.05-2.86 (m, 1H), 2.36- 1.78 (m, 7H). Et3N, DCM,0°C SMI-38 Preparation of propionyl-L-prolyl-L-phenylalanyl-L-glutamine (SMI-38): SMI-38 was synthesized using L-prolyl-L-phenylalanyl-L-glutamine (14b) (24 mg, 38 pmol, 1.0 eq.) and propionyl propionate (6 pL, 47 pmol, 1.2 eq.) by following the procedure from SMI-32. The crude residue was purified by reverse phase chromatography using water / MeCN + 0.1% formic acid to afford the title compound as a white solid (9 mg, 52% yield). LCMS ESI-MS m / z: = 447 [M+H]+. 1H NMR (400 MHz, METHANOL-d4) 5 = 7.32-7.18 (m, 5H), 4.59 (dd, J= 5.4, 9.4 Hz, 1H), 4.46 - 4.23 (m, 2H), 3.60-3.38 (m, 2H), 3.28-3.19 (m, 1H), 3.01 (dd, J = 9.4,14.1 Hz, 1H), 2.43-2.18 (m, 4H), 2.07-1.92 (m, 3H), 1.90 -1.77 (m, 3H), 1.08 (t, J = 7.4 Hz, 3H). Preparation of methyl ((S)-2-((tert-butoxycarbonyl)amino)-3-(pyridin-3-yl)propanoyl)-L-glutaminate (16a): Compound 16a was synthesized using methyl L-glutaminate HCI (300 mg, 1.5 mmol, 1.0 eq.) and (S)-2-((tert-5 butoxycarbonyl)amino)-3-(pyridin-3-yl)propanoic acid (447 mg, 1.64 mmol, 1.1 eq.) by following the procedure from Compound 1a. The crude residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a white solid (367 mg, 60% yield). LCMS ESI-MS m / z: = 409 [M+H]+. Preparation of methyl ((S)-2-amino-3-(pyridin-3-yl)propanoyl)-L-glutaminate (16b): Compound 16b was 10 synthesized using of methyl ((S)-2-((fert-butoxycarbonyl)amino)-3-(pyridin-3-yl)propanoyl)-L-glutaminate (16a) (364 mg, 0.89 mmol, 1.0 eq) in 50% TFA / DCM by following the procedure from Compound 1b to afford the title compound without further purification as an oil (478 mg, 100% yield). LCMS ESI-MS m / z: = 309 [M+H]+. Preparation of tert-butyl (S)-2-(((S)-1-(((S)-5-amino-1-methoxy-1,5-dioxopentan-2-yl)amino)-1-oxo-3-(pyridin-3-yl)propan-2-yl)carbamoyl)pyrrolidine-1-carboxylate (16c): Compound 16c was synthesized using methyl ((S)-2-amino-3-(pyridin-3-yl)propanoyl)-L-glutaminate (16b) (150 mg, 0.28 mmol, 1.0 eq.) and (ferf-butoxycarbonyl)-L-proline (68 mg, 0.31 mmol, 1.1 eq.) by following the procedure from Compound 1a. The crude residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a white solid (141 mg, 100% yield). LCMS ESI-MS m / z: = 506 [M+H]+. Preparation of methyl ((S)-3-(pyridin-3-yl)-2-((S)-pyrrolidine-2-carboxamido)propanoyl)-L-glutaminate (16d): Compound 16d was synthesized using tert-butyl (S)-2-(((S)-1-(((S)-5-amino-1-methoxy-1,5-dioxopentan-2-yl)amino)-1 -oxo-3-(pyridin-3-yl)propan-2-yl)carbamoyl)pyrrolidine-1-carboxylate (16c) (141 mg, 0.28 mmol, 1.0 eq) in 50% TFA / DCM by following the procedure from Compound 1b to afford the title compound without further purification as an oil (177 mg, 100% yield). LCMS ESI-MS m / z: = 405 [M+H]+. Preparation of methyl ((S)-2-((S)-1-propionylpyrrolidine-2-carboxamido)-3-(pyridin-3-yl)propanoyl)-L-glutaminate (16e): Compound 16e was synthesized using methyl ((S)-3-(pyridin-3-yl)-2-((S)-pyrrolidine-2-carboxamido)propanoyl)-L-glutaminate (16d) (59 mg, 93 pmol, 1.0 eq.) and propionic acid (8.4 pL, 0.11 mol, 1.2 eq.) by following the procedure from Compound 1a. The crude residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a white solid (35 mg, 83% yield). LCMS ESI-MS m / z: = 462 [M+H]+ Preparation of ((S)-2-((S)-1-propionylpyrrolidine-2-carboxamido)-3-(pyridin-3-yl)propanoyl)-L-glutamine (SMI- 23): SMI-23 was synthesized using methyl ((S)-2-((S)-1 -propionylpyrrolidine-2-carboxamido)-3-(pyridin-3- yl)propanoyl)-L-glutaminate (16e) (34 mg, 75 pmol, 1.0 eq.) by following the procedure from Compound 9d. The crude residue was purified by reverse phase chromatography using water / MeCN + 0.1% formic acid to afford the title compound as a white solid (7.5 mg, 20% yield). LCMS ESI-MS m / z: = 448 [M+H]+. 1H NMR (400 MHz, METHANOL-d4) 5 = 8.51 - 8.36 (m, 2H), 8.23 - 8.09 (m, 1H), 7.82 (br d, J = 7.8 Hz, 1H), 7.39 (br dd, J = 5.2, 7.3 Hz, 1H), 4.64 (dd, J =5.7, 8.7 Hz, 1H), 4.45-4.30 (m, 2H), 3.64-3.45 (m, 2H), 3.26 (brd, 0 = 5.4 Hz, 1H), 3.12-2.91 (m, 1H), 2.43-2.16 (m, 5H), 2.13-1.72 (m, 5H), 1.09 (t, J= 7.4 Hz, 3H). 17a Preparation of methyl ((S)-2-((S)-1-(but-2-ynoyl)pyrrolidine-2-carboxamido)-3-(pyridin-3-yl)propanoyl)-L-glutaminate (17a): Compound 17a was synthesized using methyl ((S)-3-(pyridin-3-yl)-2-((S)-pyrrolidine-2-carboxamido)propanoyl)-L-glutaminate (16d) (59 mg, 93 pmol, 1.0 eq.) and 2-butynoic acid (9.6 mg, 0.11 mol, 1.2 eq.) by following the procedure from Compound 1a. The crude residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a white solid (30 mg, 67% yield). LCMS ESI-MS m / z: = 472 [M+H]+. SMI-25 Preparation of methyl ((S)-2-((S)-1-(but-2-ynoyl)pyrrolidine-2-carboxamido)-3-(pyridin-3-yl)propanoyl)-L-glutaminate (SMI-25): SMI-25 was synthesized using methyl ((S)-2-((S)-1-(but-2-ynoyl)pyrrolidine-2-carboxamido)-3-(pyridin-3-yl)propanoyl)-L-glutaminate (17a) (28 mg, 60 pmol, 1.0 eq.) by following the procedure from Compound 9d. The crude residue was purified by reverse phase chromatography using water / MeCN + 0.1 % formic acid to afford the title compound as a white solid (15.5 mg, 50% yield). LCMS ESI-MS m / z: = 458 [M+H]+. 1H NMR (400 MHz, METHANOL-d4) 5 = 8.53 - 8.43 (m, 1H), 8.42 - 8.35 (m, 1H), 7.88 - 7.78 (m, 1H), 7.42 - 7.33 (m, 1H), 4.75 - 4.64 (m, 1H), 4.40 - 4.33 (m, 1H), 4.32 - 4.22 (m, 1H), 3.73 (t, J = 6.6 Hz, 1H), 3.60 - 3.43 (m, 1H), 3.29 - 3.23 (m, 1H), 3.09 - 2.94 (m, 1H), 2.32 - 2.13 (m, 4H), 2.11 - 1.99 (m, 3H), 1.96 - 1.80 (m, 4H). MesSnOH DCE, 70 °C Preparation of methyl N2-(tert-butoxycarbonyl)-N5,N5-dimethyl-L-glutaminate (9a): Compound 9a was synthesized using N-boc-L-glutamic acid methyl ester (1.0 g, 3.7 mmol, 1.0 eq.) and dimethylamine (2.04 mL, 4.1 5 mmol, 1.1 eq.) by following the procedure from Compound 1a. The crude residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a colorless oil (1.07 g, 100% yield). LCMS ESI-MS m / z: = 289 [M+H]+. I h2n^Y°^ o 9b Preparation of methyl N5,N5-dimethyl-L-glutaminate (9b): Compound 9b was synthesized using methyl N2-(tert- 10 butoxycarbonyl)-N5,N5-dimethyl-L-glutaminate (9a) (1.07 g, 4.8 mmol, 1.0 eq.) in 30% TFA / DCM by following the procedure from Compound 1b. The residue was purified by silica gel chromatography using DCM / MeOH +1% NH4OH as the gradient to afford the title compound as a colorless oil (813 mg, 90% yield). LCMS ESI-MS m / z: = 189 [M+H]+. Preparation of methyl N2-(tert-butoxycarbonyl)-L-leucyl-L-phenylalanyl-N5,N5-dimethyl-L-glutaminate (9c): Compound 9c was synthesized using methyl N5,N5-dimethyl-L-glutaminate (9b) (70 mg, 0.18 mmol, 1.0 eq.) and (ferf-butoxycarbonyl)-L-leucyl-L-phenylalanine (lnt-1) (35.2 mg, 0.18 mmol, 1.0 eq.) by following the procedure from Compound 1a. The residue was purified by silica gel chromatography using hexane / ethyl acetate as the gradient to afford the title compound as a white solid (77 mg, 76% yield). LCMS ESI-MS m / z: = 549 [M+H]+. I 9d Preparation of N2-(fert-butoxycarbonyl)-L-leucyl-L-phenylalanyl-N5,N5-dimethyl-L-glutamine (9d): To a solution of methyl N2-(ferf-butoxycarbonyl)-L-leucyl-L-phenylalanyl-N5,N5-dimethyl-L-glutaminate (9c) (77 mg, 0.15 mmol, 1.0 eq.) in DCE (1 mL) was added trimethyltin hydroxide (80.5 mg, 0.44 mmol, 3.0 eq.). The reaction was heated to 60 °C for 12 h. After completion, the reaction mixture was concentrated and then diluted with ethyl acetate (10 mL), followed by washing with 1 M HCI (5 mL x 3), water (5 mL), sat. NaCI solution (5 mL), dried with Na2SO4, filtered, and concentrated to afford the title compound without further purification (105 mg, 100% yield). LCMS ESI-MS m / z: = 535 [M+H]+. Preparation of N2-L-leucyl-L-phenylalanyl-N5,N5-dimethyl-L-glutamine (9e): Compound 9e was synthesized using N2-(ferf-butoxycarbonyl)-L-leucyl-L-phenylalanyl-N5,N5-dimethyl-L-glutamine (9d) (19 mg, 0.036 mmol, 1.0 eq.) in 30% TFA / DCM by following the procedure from Compound 1b to afford the title compound without further purification (15.4 mg, 100% yield). LCMS ESI-MS m / z: = 435 [M+H]+. Preparation of N2-acryloyl-L-leucyl-L-phenylalanyl-N5,N5-dimethyl-L-glutamine (SMI-30): SMI-30 was synthesized using N2-L-leucyl-L-phenylalanyl-N5,N6-dimethyl-L-glutamine (9e) (15.4 mg, 37 |jmol, 1.0 eq.) and acryloyl chloride (4.5 pL, 55 pmol, 1.5 eq.) by following the procedure from SMI-32. The crude residue was purified by reverse phase chromatography using water / MeCN +0.1% formic acid as the gradient to afford the title compound as a white solid (2.1 mg, 12% yield). LCMS ESI-MS m / z: = 489 [M+H]+. ^H NMR (400 MHz, METHANOL-d4) 5 = 7.24 (d, J = 4.4 Hz, 5H), 6.29 - 6.21 (m, 2H), 5.68 (dd, J = 3.1, 8.9 Hz, 1H), 4.65 - 4.56 (m, 2H), 4.49-4.40 (m, 1H), 4.40-4.30 (m, 1H), 3.24-3.12 (m, 1H), 3.14 (s, 1H), 3.03 (s, 4H), 2.92 (s, 4H), 2.40 (s, 5    3H), 2.25-2.12 (m, 1H), 2.04-1.88 (m, 1H), 1.52 (br d, J= 7.5 Hz, 4H), 0.91 (dd, J= 6.4, 15.6 Hz, 6H). HATU, DIPEA DMF, rt o ?°c HC>\^ / TFA DCM, rt 18d Et3N, DCM, rt Preparation of tert-butyl (S)-2-(((S)-1-methoxy-1-oxo-3-phenylpropan-2-yl)carbamoyl)pyrrolidine-1- 10 carboxylate (18a): Compound 18a was synthesized using L-phenylalanine methyl ester hydrochloride (600 mg, 2.8 mmol, 1.0 eq.) and (fert-butoxycarbonyl)-L-proline (607 mg, 2.8 mmol, 1.0 eq.) by following the procedure from Compound 1a. The crude residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a white solid (987 mg, 94% yield). LCMS ESI-MS m / z: = 377 [M+H]+. 15 Preparation of (tert-butoxycarbonyl)-L-prolyl-L-phenylalanine (18b): Compound 18b was synthesized using L-tert-butyl (S)-2-(((S)-1-methoxy-1-oxo-3-phenylpropan-2-yl)carbamoyl)pyrrolidine-1-carboxylate (18a) (200 mg, 0.53 mmol, 1.0 eq.) by following the procedure from Compound 9d to afford the title compound without further purification (257 mg, 100% yield). LCMS ESI-MS m / z: = 363 [M+H]+. Preparation of tert-butyl (S)-2-(((S)-1-(((S)-5-amino-1-methoxy-1,5-dioxopentan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)carbamoyl)pyrrolidine-1-carboxylate (18c): Compound 18c was synthesized using (tert-butoxycarbonyl)-L-prolyl-L-phenylalanine (18b) (64.3 mg, 0.18 mmol, 1.0 eq.) and L-glutamine methyl ester hydrochloride (35.2 mg, 0.18 mmol, 1.0 eq.) by following the procedure from Compound 1a. The crude residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a white solid (88.4 mg, 99% yield). LCMS ESI-MS m / z: = 505 [M+H]+. Preparation of methyl L-prolyl-L-phenylalanyl-L-glutaminate (18d): Compound 18d was synthesized using tertbutyl (S)-2-(((S)-1-(((S)-5-amino-1-methoxy-1,5-dioxopentan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)carbamoyl)pyrrolidine-1-carboxylate (18c) (85 mg, 0.17 mmol, 1.0 eq.) in 30% TFA / DCM by following the procedure from Compound 1b to afford the title compound without further purification (68.1 mg, 100% yield). LCMS ESI-MS m / z: = 405 [M+H]+. Preparation of methyl acryloyl-L-prolyl-L-phenylalanyl-L-glutaminate (SMI-31): SMI-31 was synthesized using methyl L-prolyl-L-phenylalanyl-L-glutaminate (18d) (34 mg, 0.84 mmol, 1.0 eq.) and acrylic anhydride (14 pL, 0.13 mmol, 1.5 eq.) by following the procedure from SMI-32. The crude residue was purified by reverse phase chromatography using H2O / MeCN +0.1% formic acid as the gradient to afford the title compound as a white solid (12.7 mg, 33% yield). LCMS ESI-MS m / z: = 459 [M+H]+. 1H NMR (400 MHz, METHANOL-d4) 5 = 8.20 (br d, J =7 A Hz, 1H), 7.35-7.18 (m, 5H), 6.66-6.54 (m, 1H), 6.28 (d, J= 1.8 Hz, 1H), 6.24 (d, J= 1.9 Hz, 1H), 6.12 (dd, J = 1.9, 16.7 Hz, 1H), 6.20 (br d, J = 2.0 Hz, 1H), 5.86 (dd, J= 10.5, 16.6 Hz, 1H), 5.79-5.70 (m, 1H), 5.91 -5.41 (m, 1H), 5.57 - 5.34 (m, 1H), 4.80 - 4.66 (m, 1H), 4.64 - 4.54 (m, 1H), 4.76 - 4.50 (m, 1H), 4.50 - 4.33 (m, 2H), 3.70 (s, 1H), 3.28-3.17 (m, 1H), 3.07-2.82 (m, 1H), 2.32-2.12 (m, 3H), 2.10-2.01 (m, 1H), 1.99-1.79 (m, 4H). Preparation of tert-butyl (S)-2-(((S)-1-(((S)-1-(tert-butoxy)-5-(methylamino)-1,5-dioxopentan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)carbamoyl)pyrrolidine-1 -carboxylate (19a): Compound 19a was synthesized using (fert- 5 butoxycarbonyl)-L-prolyl-L-phenylalanine (18b) (64.3 mg, 0.18 mmol, 1.0 eq.) and fert-butyl N2-((fert-butoxycarbonyl)-L-phenylalanyl)-N5-methyl-L-glutaminate (8c) (64.1 mg, 0.30 mmol, 1.7 eq.) by following the procedure from Compound 1a. The crude residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a white solid (84.3 mg, 85% yield). LCMS ESI-MS m / z: = 561 [M+H]+. 10 Preparation of N2-L-prolyl-L-phenylalanyl-N5-methyl-L-glutamine (19b): Compound 19b was synthesized using fert-butyl (S)-2-(((S)-1-(((S)-1-(fert-butoxy)-5-(methylamino)-1,5-dioxopentan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)carbamoyl)pyrrolidine-1 -carboxylate (19a) (84 mg, 0.15 mmol, 1.0 eq.) in 30% TFA / DCM by following the procedure from Compound 1b to afford the title compound without further purification (78 mg, 100% yield). LCMS ESI-MS m / z: = 405 [M+H]+. Preparation of N2-acryloyl-L-prolyl-L-phenylalanyl-N5-methyl-L-glutamine (SMI-16): SMI-16 was synthesized using N2-L-prolyl-L-phenylalanyl-N5-methyl-L-glutamine (19b) (26 mg, 50 pmol, 1.0 eq.) and acryloyl chloride (5.4 pL, 65 pmol, 1.3 eq.) by following the procedure from SMI-32. The crude residue was purified by Prep HPLC using water / MeCN + 0.1% formic acid as the gradient to afford the title compound as a white solid (10.1 mg, 44% yield). LCMS ESI-MS m / z: = 459 [M+H]+. NMR (400 MHz, METHANOL-d4) 5 = 7.32-7.18 (m, 5H), 6.62 (dd, J = 10.4, 16.8 Hz, 1H), 6.25 (dd, J= 1.8, 16.8 Hz, 1H), 5.76 (dd, J= 1.8,10.4 Hz, 1H), 4.55 (dd, J = 5.4, 9.6 Hz, 1H), 4.444.33 (m, 2H), 3.73 - 3.46 (m, 2H), 3.25 (dd, J = 5.0, 14.1 Hz, 1H), 3.02 (dd, J = 9.6, 13.9 Hz, 1H), 2.75 - 2.62 (m, 3H), 5    2.30-2.19 (m, 3H), 2.12-2.01 (m, 1H), 1.99 - 1.72 (m, 4H). Preparation of N2-but-2-ynoyl-L-prolyl-L-phenylalanyl-N5-methyl-L-glutamine (SMI-26): SMI-26 was synthesized using N2-L-prolyl-L-phenylalanyl-N5-methyl-L-glutamine (19b) (26 mg, 50 pmol, 1.0 eq.) and but-2-ynoyl chloride (5.8 pL, 65 pmol, 1.3 eq.) by following the procedure from SMI-32. The crude residue was purified by reverse 10 phase chromatography using water / MeCN + 0.1 % formic acid as the gradient to afford the title compound as a white solid (8.9 mg, 38% yield). LCMS ESI-MS m / z: = 471 [M+H]+. 1H NMR (400 MHz, METHANOL-d4) 5 = 7.39 -7.08 (m, 5H), 4.67 - 4.54 (m, 1H), 4.38 - 4.27 (m, 1H), 3.76 - 3.68 (m, 1H), 3.55 - 3.43 (m, 1H), 3.23 (br dd, J = 5.4, 14.0 Hz, 1H), 3.04-2.87 (m, 1H), 2.71 (d, J = 2.8Hz, 3H), 2.31 -2.19 (m, 3H), 2.18-2.08 (m, 1H), 2.082.03 (m, 3H), 2.03 - 1.96 (m, 1H), 1.96 - 1.75 (m, 4H). Preparation of methyl N-(((9H-fluoren-9-yl)methoxy)carbonyl)-N-methyl-L-phenylalanyl-L-glutaminate (21a): Compound 21a was synthesized using N-(((9H-fluoren-9-yl)methoxy)carbonyl)-N-methyl-L-phenylalanine (786 mg, 1.92 mmol, 1.1 eq.) and methyl L-glutaminate HCI (350 mg, 1.74 mmol, 1.0 eq.) by following the procedure from Compound 1a. The crude residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a white solid (799 mg, 84% yield). LCMS ESI-MS m / z: = 544 [M+H]+. 21b Preparation of methyl methyl-L-phenylalanyl-L-glutaminate (21b): Compound 21b was synthesized using methyl N-(((9H-fluoren-9-yl)methoxy)carbonyl)-N-methyl-L-phenylalanyl-L-glutaminate (21a) (794 mg, 1.46 mmol, 1.0 eq.) and 1-octanethiol (1.31 mL, 7.31 mmol, 5.0 eq.) by following the procedure from Compound lnt-2. The residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a white solid (294 mg, 62% yield). LCMS ESI-MS m / z: = 322 [M+H]+. 21c Preparation of tert-butyl (S)-2-(((S)-1-(((S)-5-amino-1-methoxy-1,5-dioxopentan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)(methyl)carbamoyl)pyrrolidine-1-carboxylate (21c): Compound 21c was synthesized using methyl methyl-L-phenylalanyl-L-glutaminate (21b) (50 mg, 0.16 mmol, 1.0 eq.) and (tert-butoxycarbonyl)-L-proline (41 mg, 0.19 mmol, 1.2 eq.) by following the procedure from Compound 1a. The crude residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a white solid (73.8 mg, 91% yield). LCMS ESI-MS m / z: = 519 [M+H]+. Preparation of methyl N-(L-prolyl)-N-methyl-L-phenylalanyl-L-glutaminate (21d): Compound 21d was synthesized using tert-butyl (S)-2-(((S)-1-(((S)-5-amino-1-methoxy-1,5-dioxopentan-2-yl)amino)-1-oxo-3- phenylpropan-2-yl)(methyl)carbamoyl)pyrrolidine-1-carboxylate (21c) (73.8 mg, 0.14 mmol, 1.0 eq.) in 30% TFA / DCM by following the procedure from Compound 1b to afford the title compound without further purification (75 mg, 100% yield). LCMS ESI-MS m / z: = 419 [M+H]+. SMI-28 Preparation of methyl N-(acryloyl-L-prolyl)-N-methyl-L-phenylalanyl-L-glutaminate (SMI-28): SMI-28 was synthesized using methyl N-(L-prolyl)-N-methyl-L-phenylalanyl-L-glutaminate (21d) (25.2 mg, 0.047 mmol, 1.0 eq.) and acryloyl chloride (5.1 pL, 62 pmol, 1.3 eq.) by following the procedure from SMI-32. The crude residue was 5 purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a white solid (19.9 mg, 89% yield). LCMS ESI-MS m / z: = 495 [M+Na]* NMR (400 MHz, METHANOL-d4) 6 = 7.35 - 7.23 (m, 5H), 6.68 - 6.42 (m, 1H), 6.24 (dd, J = 2.0, 16.8 Hz, 1H), 5.81 - 5.65 (m, 1H), 5.15 (dd, J = 3.5, 11.5 Hz, 1H), 4.79 -4.62 (m, 1H), 4.52-4.33 (m, 1H), 3.75-3.72 (m, 3H), 3.66-3.52 (m, 2H), 3.27-3.17 (m, 1H), 3.09-2.99 (m, 1H), 2.97 - 2.89 (m, 3H), 2.43 - 2.22 (m, 3H), 2.18 - 2.02 (m, 2H), 1.96 -1.85 (m, 1H), 1.82 - 1.63 (m, 1H), 1.12 - 0.98 10    (m, 1H), 0.91-0.77 (m,1H). SMI-28                                         SMI-20 Preparation of N-(acryloyl-L-prolyl)-N-methyl-L-phenylalanyl-L-glutamine (SMI-20): SMI-20 was synthesized using methyl N-(acryloyl-L-prolyl)-N-methyl-L-phenylalanyl-L-glutaminate (SMI-28) (18.8 mg, 0.040 mmol, 1.0 eq) by following the procedure from Compound 9d. The crude residue was purified by Prep HPLC using water / MeCN + 15    0.1% formic acid as the gradient to afford the title compound as a white solid (8.0 mg, 44% yield). LCMS ESI-MS m / z: = 481 [M+Na]* 1H NMR (400 MHz, METHANOL-d4) 5 = 7.47 - 7.11 (m, 5H), 6.71 - 6.42 (m, 1H), 6.32 - 6.15 (m, 1H), 5.79-5.60 (m, 1H), 5.15 (dd, J = 3.3, 11.4 Hz, 1H), 4.68-4.62 (m, 1H), 4.52 - 4.34 (m, 1H), 3.83-3.55 (m, 2H), 3.25-3.17 (m, 1H), 3.10-2.99 (m, 1H), 2.99-2.87 (m, 3H), 2.43-2.23 (m, 3H), 2.22-2.06 (m, 2H), 1.96 -1.85 (m, 1H), 1.72-1.61 (m, 1H), 1.15-0.94 (m, 1H), 0.92-0.75(m, 1H). Preparation of methyl N2-(N-(((9H-fluoren-9-yl)methoxy)carbonyl)-N-rnethyl-L-phenylalanyl)-N5-rnethyl-L-glutaminate (23a): Compound 23a was synthesized using N-(((9H-fluoren-9-yl)methoxy)carbonyl)-N-methyl-L- 5 phenylalanine (259 mg, 0.63 mmol, 1.1 eq.) and tert-butyl N5-methyl-L-glutaminate (8c) (100 mg, 0.57 mmol, 1.0 eq.) by following the procedure from Compound 1a. The residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a white solid (202 mg, 63% yield). LCMS ESI-MS m / z: = 558 [M+H]+. 10 Preparation of methyl N5-methyl-N2-(methyl-L-phenylalanyl)-L-glutaminate (23b): Compound 23b was synthesized using methyl N2-(N-(((9H-fluoren-9-yl)methoxy)carbonyl)-N-methyl-L-phenylalanyl)-N5-methyl-L-glutaminate (23a) (202 mg, 0.36 mmol, 1.0 eq.) and 1-octanethiol (0.32 mL, 1.81 mmol, 5.0 eq.) and 1-octanethiol (0.32 mL, 1.81 mmol, 5.0 eq.) by following the procedure from Compound lnt-2 The residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a white solid (72.5 mg, 60% 15 yield). LCMS ESI-MS m / z: = 336 [M+H]+. Preparation of tert-butyl (S)-2-(((S)-1-(((S)-1-methoxy-5-(methylamino)-1,5-dioxopentan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)(methyl)carbamoyl)pyrrolidine-1-carboxylate (23c): Compound 23c was synthesized using methyl N6-methyl-N2-(methyl-L-phenylalanyl)-L-glutaminate (23b) (30 mg, 89 pmol, 1.0 eq.) and (tert- 5 butoxycarbonyl)-L-proline (23.6 mg, 0.11 mmol, 1.2 eq.) by following the procedure from Compound 1a. The crude residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a white solid (48 mg, 99% yield). LCMS ESI-MS m / z: = 555 [M+Na]+. 23d Preparation of methyl N2-(N-(L-prolyl)-N-methyl-L-phenylalanyl)-N5-methyl-L-glutaminate (23d): Compound 10    23d was synthesized using tert-butyl (S)-2-(((S)-1-(((S)-1-methoxy-5-(methylamino)-1,5-dioxopentan-2-yl)amino)-1- oxo-3-phenylpropan-2-yl)(methyl)carbamoyl)pyrrolidine-1-carboxylate (23c) (47.6 mg, 89 pmol, 1.0 eq.) in 30% TFA / DCM by following the procedure from Compound 1b to afford the title compound without further purification (49 mg, 100% yield). LCMS ESI-MS m / z: = 433 [M+H]+. 23e 15 Preparation of methyl N2-(N-(acryloyl-L-prolyl)-N-methyl-L-phenylalanyl)-N5-methyl-L-glutaminate (23e): Compound 23e was synthesized using methyl N2-(N-(L-prolyl)-N-methyl-L-phenylalanyl)-N5-methyl-L-glutaminate (23d) (24.4 mg, 45 pmol, 1.0 eq.) and acryloyl chloride (4.8 pL, 58 pmol, 1.3 eq.) by following the procedure from SMI-32. The residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a white solid (19.1 mg, 88% yield). LCMS ESI-MS m / z: = 509 [M+Na]+. SMI-19 Preparation of N2-(N-(acryloyl-L-prolyl)-N-methyl-L-phenylalanyl)-N5-methyl-L-glutamine (SMI-19): SMI-19 was synthesized using methyl N-(L-prolyl)-N-methyl-L-phenylalanyl-L-glutaminate (23e) (17.9 mg, 37 pmol, 1.0 eq.) by following the procedure from Compound 9d. The crude residue was purified by Prep HPLC using water / MeCN + 5    0.1% formic acid as the gradient to afford the title compound as a solid (9.1 mg, 52% yield). LCMS ESI-MS m / z: = 495 [M+Na]+. 1H NMR (400 MHz, METHANOL-d4) 3 = 7.39 - 7.16 (m, 5H), 6.68 - 6.45 (m, 1H), 6.22 (dd, J = 2.0, 16.8 Hz, 1H), 5.80 - 5.65 (m, 1H), 5.15 (dd, J= 3.3, 11.4 Hz, 1H), 4.78 - 4.60 (m, 1H), 4.50 - 4.31 (m, 1H), 3.82 -3.57 (m, 2H), 3.29 - 3.16 (m, 1H), 3.09 - 2.99 (m, 1H), 2.95 - 2.88 (m, 3H), 2.67 (s, 3H), 2.40 - 2.20 (m, 3H), 2.172.02 (m, 2H), 1.94- 1.84 (m, 1H), 1.80- 1.62 (m, 1H), 1.12-0.91 (m, 1H), 0.91 -0.73 (m, 1H). Preparation of tert-butyl (R)-2-(((S)-1-(((S)-5-amino-1-(tert-butoxy)-1,5-dioxopentan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)carbamoyl)pyrrolidine-1-carboxylate (24a): Compound 24a was synthesized using tert-butyl L-phenylalanyl-L-glutaminate (lnt-2) (85 mg, 0.24 mmol, 1.0 eq.) and (fert-butoxycarbonyl)-D-proline (63 mg, 0.29 15 mmol, 1.2 eq.) by following the procedure from Compound 1a. The crude residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a white solid (122 mg, 91% yield). LCMS ESI-MS m / z: = 547 [M+H]+. Preparation of D-prolyl-L-phenylalanyl-L-glutamine (24b): Compound 24b was synthesized using fert-butyl (R)-2-(((S)-1-(((S)-5-amino-1-(te / f-butoxy)-1 l5-dioxopentan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)carbamoyl)pyrrolidine-1-carboxylate (24a) (120 mg, 0.22 mmol, 1.0 eq.) in 30% TFA / DCM by following the procedure from Compound 1b to afford the title compound without further purification as an oil (136 mg, 100% yield). LCMS ESI-MS m / z: = 391 [M+H]+. Preparation of acryloyl-D-prolyl-L-phenylalanyl-L-glutamine (SMI-36): SMI-36 was synthesized using D-prolyl-L-phenylalanyl-L-glutamine (24b) (90 mg, 0.14 mmol, 1.0 eq.) and acrylyl chloride (15 pL, 0.19 mmol, 1.3 eq.) by following the procedure from SMI-32. The crude residue was purified by reverse phase chromatography using water / MeCN + 0.1% formic acid as the gradient to afford the title compound as a white solid (26 mg, 40% yield). LCMS ESI-MS m / z: = 445 [M+H]+. 1H NMR (400 MHz, METHANOL-d4) 5 = 9.21 -9.04 (m, 1H), 8.96 (d, J= 7.6 Hz, 1H), 8.13-7.97 (m, 5H), 7.48-7.34 (m, 1H), 7.04-6.81 (m, 2H), 6.55-6.44 (m, 1H), 5.39-5.18 (m, 1H), 5.164.93 (m, 2H), 4.02 - 3.77 (m, 1H), 3.66 - 3.41 (m, 2H), 3.02 - 2.75 (m, 4H), 2.74 - 2.51 (m, 4H), 2.39 - 2.29 (m, 1H), 2.27-2.16 (m, 1H). Preparation of propionyl-D-prolyl-L-phenylalanyl-L-glutamine (SMI-39): SMI-39 was synthesized using D-prolyl-L-phenylalanyl-L-glutamine (24b) (48 mg, 77 pmol, 1.0 eq.) and propionyl propionate (12 pL, 93 pmol, 1.2 eq.) by following the procedure from SMI-32. The crude residue was purified by reverse phase chromatography using water / MeCN + 0.1% formic acid to afford the title compound as a white solid (30 mg, 86% yield). LCMS ESI-MS m / z: = 447 [M+H]+. 1H NMR (400 MHz, METHANOL-d4) 5 = 8.98 (d, J = 8.8 Hz, 1H), 8.93 (br d, J = 7.6 Hz, 1H), 8.12 -7.97 (m, 5H), 7.69 - 7.48 (m, 1H), 5.33 - 5.22 (m, 1H), 5.09 - 4.94 (m, 2H), 4.01 - 3.83 (m, 1H), 3.59 (dt, J = 10.9, 14.2 Hz, 1H), 3.09 - 2.93 (m, 3H), 2.90 - 2.76 (m, 2H), 2.72 - 2.50 (m, 4H), 2.46 - 2.29 (m, 2H), 1.75 (t, J = 7.4 Hz, 3H). Preparation of tert-butyl (S)-2-(((S)-1-(((S)-5-amino-1-(tert-butoxy)-1,5-dioxopentan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)carbamoyl)-2-methylpyrrolidine-1-carboxylate (26a): Compound 26a was synthesized using 5 tert-butyl L-phenylalanyl-L-glutaminate (lnt-2) (54 mg, 0.16 mmol, 1.0 eq.) and (S)-1-(tert-butoxycarbonyl)-2-methylpyrrolidine-2-carboxylic acid (39 mg, 0.17 mmol, 1.1 eq.) by following the procedure from Compound 1a. The crude residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a white solid (70 mg, 81% yield). LCMS ESI-MSm / z: = 561 [M+H]+. 26b 10 Preparation of ((S)-2-methylpyrrolidine-2-carbonyl)-L-phenylalanyl-L-glutamine (26b): Compound 26b was synthesized using tert-butyl (S)-2-(((S)-1-(((S)-5-amino-1-(tert-butoxy)-1,5-dioxopentan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)carbamoyl)-2-methylpyrrolidine-1-carboxylate (26a) (70 mg, 0.13 mmol, 1.0 eq.) in 30% TFA / DCM by following the procedure from Compound 1b to afford the title compound without further purification as an oil (79 mg, 100% yield). LCMS ESI-MS m / z: = 405 [M+H]+. ]_5                                                                       SMI-35 Preparation of ((S)-1-acryloyl-2-methylpyrrolidine-2-carbonyl)-L-phenylalanyl-L-glutamine (SMI-35): SMI-35 was synthesized using ((S)-2-methylpyrrolidine-2-carbonyl)-L-phenylalanyl-L-glutamine (26b) (60 mg, 95 pmol, 1.0 eq.) and acrylyl chloride (10 pL, 0.12 mmol, 1.3 eq.) by following the procedure from SMI-32. The crude residue was purified by reverse phase chromatography using water / MeCN +0.1% formic acid to afford the title compound as a white solid (14 mg, 32% yield). LCMS ESI-MS m / z: = 459 [M+H]+. 1H NMR (400 MHz, METHANOL-d4) 5 = 7.82 (br d, J = 8.6 Hz, 1H), 7.33 - 7.16 (m, 5H), 6.65 - 6.53 (m, 1H), 6.36 - 6.14 (m, 1H), 5.84 - 5.65 (m, 1H), 4.82 - 4.60 (m, 1H), 4.56 - 4.30 (m, 1H), 3.84 - 3.57 (m, 2H), 3.40 - 3.33 (m, 2H), 3.00 - 2.74 (m, 1H), 2.43 - 2.18 (m, 3H), 1.98 -1.83 (m, 1H), 1.82- 1.62 (m, 2H), 1.56 - 1.40 (m, 3H), 1.32 (q, J = 7.3 Hz, 1H). Preparation of ((S)-2-methyl-1-propionylpyrrolidine-2-carbonyl)-L-phenylalanyl-L-glutamine (SMI-37): SMI-37 was synthesized using ((S)-2-methylpyrrolidine-2-carbonyl)-L-phenylalanyl-L-glutamine (26b) (27 mg, 42 pmol, 1.0 eq.) and propionyl propionate (6.5 pL, 51 pmol, 1.2 eq.) by following the procedure from SMI-32. The crude residue was purified by reverse phase chromatography using water / MeCN +0.1% formic acid to afford the title compound as 10 a white solid (8.5 mg, 43% yield). LCMS ESI-MS m / z: = 461 [M+H]+. 1H NMR (400 MHz, METHANOL-d4) 5 = 7.53 (br d, J = 8.4 Hz, 1H), 7.31 - 7.18 (m, 5H), 4.82 - 4.66 (m, 1H), 4.35 (dd, J = 4.4, 8.9 Hz, 1H), 3.69 - 3.48 (m, 2H), 3.35 -3.30 (m, 1H), 2.96 (dd, J= 10.3,14.1 Hz, 1H), 2.41-2.20 (m, 5H), 2.14-1.97 (m, 1H), 1.97-1.81 (m, 1H), 1.791.63 (m, 3H), 1.45 (s, 3H), 1.05 (t, J - 7.4 Hz, 3H). SMI-27 28a Preparation of methyl (S)-4-(N-rnethylcarbarnoyl)-2-[(tert-butyl)(oxycarbonylamino)]butyrate (28a): Compound 28a was synthesized using (S)-4-((ferf-butoxycarbonyl)amino)-5-methoxy-5-oxopentanoic acid (1.5 g, 5.57 mmol, 1.0 eq.) and methyl amine (2 M in MeOH, 2.8 mL, 5.57 mmol, 1.0 eq.) by following the procedure from Compound 1a. The crude residue was purified by silica gel chromatography using DCM / MeOH to afford the title compound as a red-oil (1.5 g, 100% yield). LCMS ESI-MS m / z: = 175 [M+H-100]+. Preparation of methyl (S)-4-(N-methylcarbamoyl)-2-aminobutyrate TFA (28b): Compound 28b was synthesized 5 using methyl (S)-4-(N-methylcarbamoyl)-2-[(ferf-butyl)(oxycarbonylamino)]butyrate (28a) (1.53 g, 5.6 mmol, 1.0 eq.) in 50% TFA / DCM by following the procedure from Compound 1b to afford the title compound without any further purification as an orange oil (1.6 g, 100% yield). LCMS ESI-MS m / z: = 175 [M+H]+. i O^NH B°C i H g 28c Preparation of methyl (S)-4-(N-methylcarbamoyl)-2-{(S)-2-[(tert-butyl)(oxycarbonylamino)]-3- 10 phenylpropionylaminojbutyrate (28c): Compound 28c was synthesized using methyl (S)-4-(N-methylcarbamoyl)-2-aminobutyrate TFA (28b) (322 mg, 1.12 mmol, 1.0 eq.) and (S)-2-[(ferf-butyl)(oxycarbonylamino)]-3-phenylpropionic acid (326 mg, 1.23 mmol, 1.1 eq.) by following the procedure from Compound 1a. The crude residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a white solid (224 mg, 48% yield). LCMS ESI-MS m / z: = 422 [M+H]+. I °^NH o I ° 25                                                                   28d Preparation of methyl (S)-4-(N-methylcarbamoyl)-2-[(S)-2-amino-3-phenylpropionylamino]butyrate (28d): Compound 28d was synthesized using methyl (S)-4-(N-methylcarbamoyl)-2-{(S)-2-[(tert-butyl)(oxycarbonylamino)]-3-phenylpropionylaminojbutyrate (28c) (224 mg, 0.53 mmol, 1.0 eq.) in 50% TFA / DCM by following the procedure from Compound 1b to afford the title compound without further purification as an oil (231 mg, 100% yield). LCMS ESI-MS 20 m / z: = 322 [M+H]+. Preparation of tert-butyl (S)-2-(((S)-1-(((S)-1-methoxy-5-(methylamino)-1,5-dioxopentan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)carbamoyl)-2-methylpyrrolidine-1-carboxylate (28e): Compound 28e was synthesized using methyl (S)-4-(N-methylcarbamoyl)-2-[(S)-2-amino-3-phenylpropionylamino]butyrate (28d) (77 mg, 0.17 mmol, 1.0 eq.) and (S)-1-(fert-butoxycarbonyl)-2-methylpyrrolidine-2-carboxylic acid (49 mg, 0.21 mmol, 1.2 eq.) by following the procedure from Compound 1b. The crude residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a white solid (76 mg, 81% yield). LCMS ESI-MS m / z: = 533 [M+H]+. Preparation of methyl (S)-4-(N-methylcarbamoyl)-2-{(S)-2-[(S)-2-methyl-2-pyrrolidinylcarbonylamino]-3-phenylpropionylamino}butyrate (28f): Compound 28f was synthesized using fert-butyl (S)-2-(((S)-1-(((S)-1-methoxy-5-(methylamino)-1,5-dioxopentan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)carbamoyl)-2-methylpyrrolidine-1-carboxylate (28e) in 50% TFA / DCM by following the procedure from Compound 1b to afford the title compound without further purification as an oil (78 mg, 100% yield). LCMS ESI-MS m / z: = 433 [M+H]+. I O^NH CV'A'i ' ” V 0 SMI-27 Preparation of methyl (S)-4-(N-methylcarbamoyl)-2-{(S)-2-[(S)-1-acryloyl-2-methyl-2- pyrrolidinylcarbonylamino]-3-phenylpropionylamino}butyrate (SMI-27): SMI-27 was synthesized using methyl (S)-4-(N-methylcarbamoyl)-2-{(S)-2-[(S)-2-methyl-2-pyrrolidinylcarbonylamino]-3-phenylpropionylamino}butyrate (28f) (39 mg, 72 pmol, 1.0 eq.) and acrylyl chloride (7.8 pL, 93 pmol, 1.3 eq.) by following the procedure from SMI-32. The crude residue was purified silica gel purification using DCM / MeOH as the gradient to afford the title compound as a white solid (27 mg, 79% yield). LCMS ESI-MS m / z: = 487 [M+H]+. 1H NMR (400 MHz, METHANOL-d4) 5 = 7.32 -7.14 (m, 5H), 6.59 (dd, J= 10.4, 16.8 Hz, 1H), 6.21 (dd, J= 1.9, 16.8 Hz, 1H), 5.73 (dd, J = 1.8, 10.4 Hz, 1H), 4.71 (dd, J= 4.6, 10.6 Hz, 1H), 4.33 (dd, J = 4.8, 8.8 Hz, 1H), 3.83-3.74 (m, 1H), 3.71 (s, 3H), 3.70-3.65 (m, 1H), 2.91 (dd, J = 10.6, 14.1 Hz, 1H), 2.69 (s, 3H), 2.34 - 2.13 (m, 4H), 2.10 - 1.97 (m, 1H), 1.95 - 1.83 (m, 1H), 1.80-1.64 (m, 3H), 1.48 (s, 3H). SMI-27 Me3SnOH DCE, 60 °C SMI-17 5 Preparation of (S)-4-(N-methylcarbamoyl)-2-{(S)-2-[(S)-1-acryloyl-2-methyl-2-pyrrolidinylcarbonylamino]-3-phenylpropionylamino}butyric acid (SMI-17): SMI-17 was synthesized using methyl (S)-4-(N-methylcarbamoyl)-2-{(S)-2-[(S)-1 -acryloyl-2-methyl-2-pyrrolidinylcarbonylamino]-3-phenylpropionylamino}butyrate (SMI-27) (26 mg, 57 pL, 1.0 eq.) by following the procedure from Compound 9d. The crude residue was purified by Prep HPLC using water / MeCN + 0.1% formic acid as the gradient to afford the title compound as a white solid (19 mg, 73% yield). 10 LCMS ESI-MS m / z: = 473 [M+H]+. 1H NMR (400 MHz, METHANOL-d^ 5 = 7.72 (br d, J = 8.4 Hz, 1H), 7.36-7.12 (m, 5H), 6.59 (dd, J= 10.4,16.8 Hz, 1H), 6.22 (dd, J= 1.8, 16.8 Hz, 1H), 5.73 (dd, J= 1.8,10.4 Hz, 1H), 4.74 (ddd, J = 4.6, 8.4, 10.5 Hz, 1H), 4.31 (dd, J = 4.4, 8.9 Hz, 1H), 3.80 - 3.64 (m, 2H), 3.38 (d, J = 4.5 Hz, 1H), 2.94 (dd, J = 10.6, 14.1 Hz, 1H), 2.76-2.66 (m, 3H), 2.36-2.16 (m, 3H), 2.11-2.00 (m, 1H), 1.96-1.84 (m, 1H), 1.80-1.64 (m, 3H), 1.49 (s, 3H). Preparation of tert-butyl (S)-3-(((S)-1-(((S)-5-amino-1-(tert-butoxy)-1,5-dioxopentan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)carbamoyl)pyrrolidine-1-carboxylate (32a): Compound 32a was synthesized using tert-butyl L-phenylalanyl-L-glutaminate (lnt-2) (100 mg, 0.28 mmol, 1.0 eq.) and (S)-1 -(tert-butoxycarbonyl)pyrrolidine-3-carboxylic acid (67.8 mg, 0.32 mmol, 1.1 eq.) by following the procedure from Compound 1a. The crude residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a white solid (150 mg, 96% yield). LCMS ESI-MS m / z: = 547 [M+H]+. Preparation of ((S)-pyrrolidine-3-carbonyl)-L-phenylalanyl-L-glutamine (32b): Compound 32b was synthesized using tert-butyl (S)-3-(((S)-1-(((S)-5-amino-1-(tert-butoxy)-1,5-dioxopentan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)carbamoyl)pyrrolidine-1 -carboxylate (32a) (150 mg, 0.28 mmol, 1.0 eq.) in 30% TFA / DCM by following the procedure from Compound 1b to afford the title compound without further purification as an oil (166 mg, 93% yield). LCMS ESI-MS m / z: = 391 [M+H]+. Preparation of ((S)-1-acryloylpyrrolidine-3-carbonyl)-L-phenylalanyl-L-glutamine (SMI-12): SMI-12 was synthesized using ((S)-pyrrolidine-3-carbonyl)-L-phenylalanyl-L-glutamine (32b) (83 mg, 0.13 mmol, 1.0 eq.) and acryloyl acrylate (20 pL, 0.17 mmol, 1.3 eq.) by following the procedure from SMI-32. The crude residue was purified by reverse phase chromatography using water / MeCN + 0.1% formic acid as the gradient to afford the title compound as a white solid (11 mg, 18% yield). LCMS ESI-MS m / z: = 445 [M+H]+. NMR (400 MHz, METHANOL-d4) 5 = 8.23 (br d, J = 7.6 Hz, 1H), 7.35 - 7.18 (m, 5H), 6.60 - 6.48 (m, 1H), 6.29 - 6.19 (m, 1H), 5.77 - 5.68 (m, 1H), 4.80 - 4.67 (m, 1H), 4.41 (dd, J= 4.4, 9.3 Hz, 1H), 3.78-3.51 (m, 3H), 3.50-3.37 (m, 1H), 3.24 (dd, J= 4.8, 14.1 Hz, 1H), 3.15 -2.96 (m, 1H), 2.86 (dd, 0=10.2, 13.9 Hz, 1H), 2.37-2.29 (m, 2H), 2.28-2.16 (m, 1H), 2.10-1.91 (m, 2H), 1.861.66 (m, 1H). Et3N, DCM, O°C Preparation of ((S)-1-propionylpyrrolidine-3-carbonyl)-L-phenylalanyl-L-glutamine (SMI-14): SMI-14 was synthesized using ((S)-pyrrolidine-3-carbonyl)-L-phenylalanyl-L-glutamine (32b) (83 mg, 0.13 mmol, 1.0 eq.) and propionyl propionate (22 pL, 0.17 mmol, 1.3 eq.) by following the procedure from SMI-32. The crude residue was purified by reverse phase chromatography using water / MeCN + 0.1 % formic acid as the gradient to afford the title 5 compound as a white solid (39 mg, 65% yield). LCMS ESI-MS m / z: = 447 [M+H]+. 1H NMR (400 MHz, METHANOL-d4) 6 = 7.20 - 7.08 (m, 5H), 4.71 - 4.52 (m, 1H), 4.31 (dd, J = 4.5, 9.3 Hz, 1H), 3.54 - 3.37 (m, 2H), 3.35 - 3.23 (m, 2H), 3.20-3.10 (m, 1H), 3.04-2.84 (m, 1H), 2.82-2.70 (m, 1H), 2.26-2.07 (m, 5H), 2.00-1.81 (m, 2H), 1.751.53 (m, 1H), 0.99 (dt, J= 3.9, 7.5 Hz, 3H). 10 Preparation of ((S)-1-(but-2-ynoyl)pyrrolidine-3-carbonyl)-L-phenylalanyl-L-glutamine (SMI-40): SMI-40 was synthesize using ((S)-pyrrolidine-3-carbonyl)-L-phenylalanyl-L-glutamine (32b) (103 mg, 0.16 mmol, 1.0 eq.) and 2-butynoyl chloride (22 mg, 0.22 mmol, 1.3 eq.) by following the procedure from SMI-32. The crude residue was purified by reverse phase chromatography using water / MeCN + 0.1 % formic acid as the gradient to afford the title compound as a white solid (10 mg, 13% yield). LCMS ESI-MS m / z: = 457 [M+H]+. 1H NMR (400 MHz, METHANOL- 15    d4) 5 = 8.32 - 8.10 (m, 1H), 7.25 - 7.08 (m, 5H), 4.71 - 4.49 (m, 1H), 4.39 - 4.23 (m, 1H), 3.83 - 3.56 (m, 2H), 3.54 - 3.34 (m, 2H), 3.20-3.09 (m, 1H), 3.04-2.89 (m, 1H), 2.83-2.71 (m, 1H), 2.27-2.19 (m, 1H), 2.17-1.99 (m, 2H), 1.95- 1.82 (m, 4H), 1.75- 1.58 (m, 1H). Preparation of tert-butyl (S)-3-(((S)-1-(((S)-5-amino-1-(tert-butoxy)-1,5-dioxopentan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)carbamoyl)pyrrolidine-1-carboxylate (35a): Compound 35a was synthesized using fert-butyl L-phenylalanyl-L-glutaminate (lnt-2) (100 mg, 0.29 mmol, 1.0 eq.) and (R)-1-(fert-butoxycarbonyl)pyrrolidine-3-carboxylic acid (68 mg, 0.31 mmol, 1.1) by following the procedure from Compound 1a. The crude residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a white solid (146 mg, 93% yield). LCMS ESI-MS m / z: = 547 [M+H]+. Preparation of ((S)-pyrrolidine-3-carbonyl)-L-phenylalanyl-L-glutamine (35b): Compound 35b was synthesized using fert-butyl (S)-3-(((S)-1-(((S)-5-amino-1-(fert-butoxy)-1,5-dioxopentan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)carbamoyl)pyrrolidine-1 -carboxylate (35a) (146 mg, 0.26 mmol, 1.0 eq.) in 30% TFA / DCM by following the procedure from Compound 1b to afford the title compound without further purification as an oil (166 mg, 100% yield). LCMS ESI-MS m / z: = 391 [M+H]+. Preparation of ((R)-1-acryloylpyrrolidine-3-carbonyl)-L-phenylalanyl-L-glutamine (SMI-13): SMI-13 was synthesized using ((S)-pyrrolidine-3-carbonyl)-L-phenylalanyl-L-glutamine (35b) (83 mg, 0.13 mmol, 1.0 eq.) and acryloyl acrylate (20 pL, 0.17 mmol, 1.3 eq.) by following the procedure from SMI-32. The crude residue was purified by reverse phase chromatography using water / MeCN + 0.1% formic acid as the gradient to afford the title compound as a white solid (13 mg, 21% yield). LCMS ESI-MS m / z: = 445 [M+H]+. NMR (400 MHz, METHANOL-d4) 6 = 8.14 (brt, J = 7.1 Hz, 1H), 7.24-7.08 (m, 5H), 6.50-6.31 (m, 1H), 6.19-6.10 (m, 1H), 5.63 (ddd, J= 1.9, 6.0, 10.4 Hz, 1H), 4.57 (dt, J = 4.9, 10.0 Hz, 1H), 4.39 - 4.24 (m, 1H), 3.63 - 3.42 (m, 3H), 3.39 - 3.23 (m, 2H), 3.20 - 3.07 (m, 1H), 3.05-2.88 (m, 1H), 2.85-2.70 (m, 1H), 2.26-2.19 (m, 2H), 2.18-1.96 (m, 2H), 1.94-1.82 (m, 1H). Preparation of ((R)-1-propionylpyrrolidine-3-carbonyl)-L-phenylalanyl-L-glutamine (SMI-15): SMI-15 was synthesized using ((S)-pyrrolidine-3-carbonyl)-L-phenylalanyl-L-glutamine (35b) (83 mg, 0.13 mmol, 1.0 eq.) and propionyl propionate (22 pL, 0.17 mmol, 1.3 eq.) by following the procedure from SMI-32. The crude residue was 5 purified by reverse phase chromatography using water / MeCN + 0.1 % formic acid as the gradient to afford the title compound as a white solid (47 mg, 78% yield). LCMS ESI-MS m / z: = 447 [M+H]+. 1H NMR (400 MHz, METHANOL-d4) 6 = 7.21 - 7.08 (m, 5H), 4.56 (ddd, J = 4.9, 9.9, 14.6 Hz, 1H), 4.40 - 4.22 (m, 1H), 3.50 - 3.32 (m, 3H), 3.20 -3.03 (m, 2H), 3.00 - 2.85 (m, 1H), 2.82 - 2.73 (m, 1H), 2.25 - 2.00 (m, 6H), 1.98 - 1.93 (m, 1H), 1.92 -1.82 (m, 1H), 1.03-0.95 (m, 3H). 37a Preparation of tert-butyl (1-((tert-butoxycarbonyl)amino)cyclopropane-1-carbonyl)-L-phenylalanyl-L-glutaminate (37a): Compound 37a was synthesized using tert-butyl L-phenylalanyl-L-glutaminate (lnt-2) (100 mg, 0.29 mmol, 1.0 eq.) and 1-((tert-butoxycarbonyl)amino)cyclopropane-1-carboxylic acid (58.2 mg, 0.29 mmol, 1.0 15 eq.) by following the procedure from Compound 1a. The residue was purified by silica gel chromatography using DCM / MeOH as the gradient to afford the title compound as a white solid (149 mg, 98% yield). LCMS ESI-MS m / z: = 533 [M+H]+. 37b Preparation of (1-aminocyclopropane-1-carbonyl)-L-phenylalanyl-L-glutamine (37b): Compound 37b was synthesized using fert-butyl (1-((fer / -butoxycarbonyl)amino)cyclopropane-1-carbonyl)-L-phenylalanyl-L-glutaminate (37a) (74 mg, 0.14 mmol, 1.0 eq.) in 30% TFA / DCM by following the procedure from Compound 1b to afford the title compound without further purification (52.3 mg, 100% yield). LCMS ESI-MS m / z: = 377 [M+H]+. Preparation of (1-acrylamidocyclopropane-1-carbonyl)-L-phenylalanyl-L-glutamine (SMI-29): SMI-29 was synthesized using (1-aminocyclopropane-1-carbonyl)-L-phenylalanyl-L-glutamine (37b) (52.3 mg, 0.14 mmol, 1.0 eq.) and acryloyl chloride (17 pL, 0.21 mmol, 1.5 eq.) by following the procedure from SMI-32. The residue was purified by reverse phase chromatography using water / MeCN +0.1% formic acid as the gradient to afford the title compound as a white solid (3.2 mg, 6% yield). LCMS ESI-MS m / z: = 431 [M+H]+. 1H NMR (400 MHz, METHANOL-d4) 5 = 7.28 - 7.16 (m, 5H), 6.31 - 6.19 (m, 2H), 5.72 (dd, J= 2.8, 9.2 Hz, 1H), 4.77 - 4.58 (m, 1H), 4.29 (dd, J = 4.1, 8.2 Hz, 1H), 3.25 - 3.19 (m, 1H), 3.10 - 3.03 (m, 3H), 2.93 (s, 2H), 2.71 (s, 1H), 2.33 -2.15 (m, 3H), 2.09 (s, 2H), 2.05-1.90 (m, 1H), 1.50 - 1.30 (m, 2H), 1.07 - 0.95 (m, 2H). Preparation of (1-propionamidocyclopropane-1-carbonyl)-L-phenylalanyl-L-glutamine (SMI-29): SMI-29 was synthesized using (1-aminocyclopropane-1-carbonyl)-L-phenylalanyl-L-glutamine (37b) (52.3 mg, 0.14 mmol, 1.0 eq.) and propionic anhydride (27 pL, 0.21 mmol, 1.5 eq.) by following the procedure from SMI-32. The residue was purified by reverse phase chromatography using water / MeCN + 0.1 % formic acid as the gradient to afford the title compound as a white solid (2.3 mg, 4% yield). LCMS ESI-MS m / z: = 433 [M+H]+. ’H NMR (400 MHz, METHANOL-d4 ) 5 = 7.48 (d, J = 7.9 Hz, 1H), 7.28-7.17 (m, 5H), 4.86 (s, 17H), 4.74-4.53 (m, 1H), 4.37 (dd, J = 4.1, 9.1 Hz, 1H), 3.17 (dd, J = 5.2, 13.9 Hz, 1H), 3.03 (dd, 0 = 7.9, 13.9 Hz, 1H), 2.33-2.14 (m, 5H), 2.08-1.90 (m, 1H), 1.46-1.28 (m, 2H), 1.07 (t, 0=7.6 Hz, 3H), 1.01 - 0.89 (m, 2H). Example 2: Binding of Recombinant Human Trim? Protein to RACO1, MSK1 and STING Without wishing to be bound by theory, it is believed that MSK1 directly phosphorylates the tripartite motif containing 7 (Trim7). It is believed, without wishing to be bound by theory, that Trim7 can ubiquitinylate proteins such as RACO1, Mitochondrial Anti-Viral Signaling Protein (MAVS) and stimulator of interferon genes (STING), which in turn impairs host immune interferon responsiveness. Genes encoding recombinant human Trim7 RAC01 and MSK1 proteins were cloned in expression vectors using standard techniques known in the art. HISe-tagged derivatives of recombinant human Trim? RAC01 and MSK1 proteins were prepared using standard techniques. These proteins had the following sequences: TRIM7-His MAAVGPRTGPGTGAEALALAAELQGEATCSICLELFREPVSVECGHSFCRACIGRCWERPGAGSVGAATRAPPFPL PCPQCREPARPSQLRPNRQLAAVATLLRRFSLPAAAPGEHGSQAAAARAAAARCGQHGEPFKLYCQDDGRAICVVC DRAREHREHAVLPLDEAVQEAKELLESRLRVLKKELEDCEVFRSTEKKESKELLKQMAAEQEKVGAEFQALRAFLVE QEGRLLGRLEELSREVAQKQNENLAQLGVEITQLSKLSSQIQETAQKPDLDFLQEFKSTLSRCSNVPGPKPTTVSSEM KNKVWNVSLKTFVLKGMLKKFKEDLRGELEKEEKVELTLDPDTANPRLILSLDLKGVRLGERAQDLPNHPCRFDTNTR VLASCGFSSGRHHWEVEVGSKDGWAFGVARESVRRKGLTPFTPEEGVWALQLNGGQYWAVTSPERSPLSCGHLS RVRVALDLEVGAVSFYAVEDMRHLYTFRVNFQERVFPLFSVCSTGTYLRIWPHHHHHH (SEQ ID NO: 17) RAC0-1-His MALPAGPAEAACALCQRAPREPVRADCGHRFCRACWRFWAEEDGPFPCPECADDCWQRAVEPGRPPLSRRLLAL EEAAAAPARDGPASEAALQLLCRADAGPLCAACRMAAGPEPPEWEPRWRKALRGKENKGSVEIMRKDLNDARDLH GQAESAAAVWKGHVMDRRKKALTDYKKLRAFFVEEEEHFLQEAEKEEGLPEDELADPTERFRSLLQAVSELEKKHR NLGLSMLLQHHHHHH (SEQ ID NO: 18) MSK1-His MEEEGGSSGGAAGTSADGGDGGEQLLTVKHELRTANLTGHAEKVGIENFELLKVLGTGAYGKVFLVRKISGHDTGKL YAMKVLKKATIVQKAKTTEHTRTERQVLEHIRQSPFLVTLHYAFQTETKLHLILDYINGGELFTHLSQRERFTEHEVQIY VGEIVLALEHLHKLGIIYRDIKLENILLDSNGHWLTDFGLSKEFVADETERAYSFCGTIEYMAPDIVRGGDSGHDKAVD WWSLGVLMYELLTGASPFTVDGEKNSQAEISRRILKSEPPYPQEMSALAKDLIQRLLMKDPKKRLGCGPRDADEIKEH LFFQKINWDDLAAKKVPAPFKPVIRDELDVSNFAEEFTEMDPTYSPAALPQSSEKLFQGYSFVAPSILFKRNAAVIDPL QFHMGVERPGVTNVARSAMMKDSPFYQHYDLDLKDKPLGEGSFSICRKCVHKKSNQAFAVKIISKRMEANTQKEITA LKLCEGHPNIVKLHEVFHDQLHTFLVMELLNGGELFERIKKKKHFSETEASYIMRKLVSAVSHMHDVGWHRDLKPEN LLFTDENDNLEIKIIDFGFARLKPPDNQPLKTPCFTLHYAAPELLNQNGYDESCDLWSLGVILYTMLSGQVPFQSHDRS LTCTSAVEIMKKIKKGDFSFEGEAWKNVSQEAKDLIQGLLTVDPNKRLKMSGLRYNEWLQDGSQLSSNPLMTPDILGS SGAAVHTCVKATFHAFNKYKREGFCLQNVDKAPLAKRRKMKKTSTSTETRSSSSESSHSSSSHSHGKTTPTKTLQPS NPADSNNPETLFQFSDSVAHHHHHH (SEQ ID NO: 19) The binding of human Trim7 protein to human RAC01 and human MSK1 proteins was studied using a Meso Scale Discovery (MSD) platform-based assay. Briefly, recombinant human Trim7 protein was coated on a plate. Increasing amounts of RAC01, MSK1, or CD47 proteins were added to the plate for capture by the plate-bound recombinant Trim? protein. The RAC01 or MSK1 proteins captured by the plate-bound Trim? protein was detected using an antihuman RAC01 or anti-human MSK1 antibodies and a SULFO-TAG conjugated secondary antibody. As shown in FIG. 1 A, RAC01 protein bound to the plate-bound recombinant Trim7 protein in a dose-dependent manner. In comparison, the CD47 protein showed only background signal (FIG. 1A). similarly, as shown in FIG. 10, MSK1 protein bound to the plate-bound recombinant Trim7 protein in a dose-dependent manner. In comparison, the CD47 protein showed only background signal (FIG. 10). These results demonstrate, inter alia, that the Trim7 protein disclosed herein specifically binds to RAC01, MSK1 proteins. The binding of human Trim7 protein to human RAC01 was confirmed in a second experiment. Briefly, recombinant human Trim7 protein was coated on a plate. Increasing amount of recombinant human RAC01 protein was added to the plate for capture by the plate-bound recombinant Trim7 protein. The recombinant human RAC01 protein captured by the plate-bound Trim7 protein was detected using an anti-human RAC01 antibody and a SULFO-TAG conjugated secondary antibody. As shown in FIG. 1B, RAC01 protein bound to the plate-bound recombinant Trim7 protein in a dose-dependent manner. These results demonstrate, inter alia, that the Trim7 protein disclosed herein specifically binds to RAC01 protein in a dose-dependent manner. The binding of human Trim7 protein to human MSK1 was confirmed in a second experiment using the recombinant human MSK1-His described herein and commercially available recombinant human MSK1-GST protein. Briefly, recombinant human Trim7 protein was coated on a plate. Increasing amounts of recombinant human MSK1-His or MSK1-GST proteins were added to the plate for capture by the plate-bound recombinant Trim7 protein. Any recombinant human MSK1 protein captured by the plate-bound Trim7 protein was detected using an anti-human MSK1 antibody and a SULFO-TAG conjugated secondary antibody. As shown in FIG. 1D, both recombinant human MSK1-His and MSK1-GST proteins bound to the plate-bound recombinant Trim7 protein in a dose-dependent manner, with nearly identical binding affinity. These results also demonstrate that the (HIS)e tag on the MSK1-His and RAC01-His proteins used in these experiments has no role in binding to Trim7. These results demonstrate, inter alia, that the Trim7 protein disclosed herein specifically binds to RAC01 protein in a dose-dependent manner. The binding of human Trim7 protein to human STING was also studied using two commercially sourced STING proteins: His-STING, which has a hexa-histidine tag at the N-terminus, and STING-cMyc, which has a cMyc tag at the C-terminus. Briefly, recombinant human Trim7 protein was coated on a plate. Increasing amounts of recombinant human His-STING and STING-cMyc proteins were added to the plate for capture by the plate-bound recombinant Trim? protein. Any recombinant human STING protein captured by the plate-bound Trim? protein was detected using an anti-human STING antibody and a SULFO-TAG conjugated secondary antibody. As shown in FIG. 1D, both His-STING and STING-cMyc proteins bound to the plate-bound recombinant Trim? protein in a dose-dependent manner, without being bound by theory, the observed lower affinity binding of recombinant Trim? to STING-cMyc may be reflective of the c-term tag interfering with the TRIM? interaction. Collectively, these results demonstrate, inter alia, that the Trim? protein disclosed herein specifically binds to RAC01, MSK1, and STING proteins in a dose-dependent manner. Example 3: Binding of Recombinant Human Trim7 Protein to Enterovirus 71 2BC Protein The binding of Trim? protein to enterovirus 71 2B / C and 2C proteins was studied using a Meso Scale Discovery (MSD) platform-based assay. For this experiment, recombinant human RAC01 and MSK1 proteins were used as positive controls and recombinant human CD47 protein was used as a negative control. Briefly, recombinant human RAC01, MSK1, CD47, enterovirus 71 2B or enterovirus 71 2BC proteins were coated on a plate. Increasing amounts of recombinant human Trim7 protein was added to the plate for capture by the plate-bound RAC01, MSK1, CD47, enterovirus 71 2B or enterovirus 71 2BC proteins. The Trim? protein captured by the plate-bound RAC01, MSK1, CD47, enterovirus 71 2B or enterovirus 71 2BC proteins was detected using an anti-human Trim? antibody and a SULFO-TAG conjugated secondary antibody. As shown in FIG. 2, Trim? was able to bind the plate-bound enterovirus 71 2B / C protein in a dose-dependent manner. As expected, Trim? was able to bind the plate-bound RAC01 and MSK1 proteins, but not CD47 protein (FIG. 2). The extent of binding of Trim? to enterovirus 71 2B / C protein approximated the levels of binding to MSK1 and RAC01. In comparison, Trim? did not noticeably bind to the 2B portion of the viral protein (FIG. 2). These results demonstrate, inter alia, that the Trim? protein disclosed herein specifically binds to enterovirus 71 2B / C protein. Example 4: Enterovirus 71 2BC Protein Disrupts the Binding of Recombinant Human Trim7 Protein to RAC01 and MSK1 The effect of enterovirus 71 2B / C protein on the binding of Trim? protein to recombinant human RAC01 or MSK1 proteins was studied using an a Meso Scale Discovery (MSD) platform-based assay. Briefly, recombinant human Trim? protein was coated on a plate. Increasing amounts of enterovirus 71 2B / C protein was added to the plate for capture by the plate-bound recombinant Trim? protein. Recombinant human MSK1 protein was added to the plate with or without 5 pg / ml enterovirus 71 2B / C protein. The binding was then detected using anti-MSK1 antibody and a SULFOTAG conjugated secondary antibody. As shown in FIG. 3A, Trim? could be detected with MSK1 protein / anti-MSK1 antibody. Interestingly, the amount of signal reduced when the detection was performed in the presence of 5 pg / ml enterovirus 71 2B / C protein (FIG. 3A). These results demonstrate, inter alia, that enterovirus 71 2BC protein disrupts the binding of recombinant human Trim7 protein to MSK1. In another such experiment, recombinant human Trim7 protein was coated on a plate. Increasing amounts of enterovirus 71 2B / C protein was added to the plate for capture by the plate-bound recombinant Trim7 protein. Recombinant human RAC01 protein was added to the plate with or without 5 pg / ml enterovirus 71 2B / C protein. The binding was then detected using anti-RAC01 antibody and a SULFO-TAG conjugated secondary antibody. As shown in FIG. 3B, Trim7 could be detected with RAC01 protein / anti-RACO1 antibody. Interestingly, the amount of signal reduced when the detection was performed in the presence of 5 pg / ml enterovirus 71 2B / C protein (FIG. 3B). These results demonstrate, inter alia, that enterovirus 71 2BC protein disrupts the binding of recombinant human T rim7 protein toRACOI. Example 5: Binding of Recombinant Human Trim? Protein to the Peptides Disclosed Herein The crystal structure of Trim7 bound to the CVB_2C (319-329) peptide (SVGTTLEALFQ), which is the C-terminal fragment of the Coxsackievirus B3 (CVB3)_2C protein is shown in FIG. 4. This structure showed binding of an 11 amino acid-long C-terminal peptide derived from coxsackievirus B3 (CVB3) 2C protein to the Trim7 protein. The binding showed, inter alia, interactions with a C-terminal Gin residue. Liang et al., Structural insights into the viral proteins binding by TRIM7 reveal a general C-terminal glutamine recognition mechanism, bioRxiv2022.03.24.485560. Binding by the recombinant human Trim7 protein to a peptide having amino acid sequence YPYDVPDYATTLEALFQ (HA-CVB3_2C(322-329)) and its derivative having amino acid sequence YPYDVPDYATTLEALFA (HA-CVB3_2C(322-Q329A)), which has a C-terminal Q to A substitution was studied. These peptides comprise a HA tag at N-terminus. Briefly, recombinant human Trim7 protein was coated on a plate. Increasing amount of HA-CVB3_2C(322-329) and HA-CVB3_2C(322-Q329A peptides were added to the plate for capture by the plate-bound recombinant Trim / protein. The HA-CVB3_2C(322-329) and HA-CVB3_2C(322-Q329A peptides captured by the plate-bound Trim7 protein were detected using an anti-HA antibody and a SULFO-TAG conjugated secondary antibody. As shown in FIG. 5A, HA-CVB3_2C(322-329) peptide bound to the plate-bound recombinant Trim7 protein in a dose-dependent manner. In contrast, HA-CVB3_2C(322-Q329A) showed background level binding or binding with extremely reduced affinity. Binding by the recombinant human Trim / protein to a peptide having amino acid sequence YPYDVPDYARKLDTYLQ (HA-GN1_2C(322-329)) and its derivative having amino acid sequence YPYDVPDYARKLDTYLQ (HA-GN1_2C(322-Q329A), which has a C-terminal Q to A substitution was studied. These peptides comprise a HA tag at N-terminus. Briefly, recombinant human Trim7 protein was coated on a plate. Increasing amount of HA-GN1_2C(322-329) and HA-GN1_2C(322-Q329A peptides were added to the plate for capture by the plate-bound recombinant Trim7 protein. The HA-GN1_2C(322-329) and HA-GN1_2C(322-Q329A peptides captured by the plate-bound Trim7 protein were detected using an anti-HA antibody and a SULFO-TAG conjugated secondary antibody. As shown in FIG. 5A, HA- GN1_2C(322-329) peptide bound to the plate-bound recombinant Trim7 protein in a dose-dependent manner. In contrast, HA-GN1_2C(322-Q329A) showed background level binding. These results demonstrate, inter alia, that that the peptides disclosed herein bind to recombinant human Trim7 in a C-terminal Gin-dependent manner, at low nM concentrations. These results further demonstrate, inter alia, that the peptides disclosed herein bind well to Trim7 when the C-terminal amino acid is Gin or a similar amino acid, and a C-terminal Ala does not support binding. These results further demonstrate, inter alia, that the peptides having a hydrophobic or aromatic amino acid at second position from C-terminus bind well to Trim7. Example 6: Disruption of the Binding of Recombinant Human Trim7 Protein to RAC01 and MSK1 The effect of the peptides disclosed herein on the binding of Trim7 protein to recombinant human RAC01, MSK1 or STING proteins is studied using an a Meso Scale Discovery (MSD) platform-based assay. Briefly, recombinant human Trim7 protein is coated on a plate. Increasing amounts of the peptides disclosed herein (e.g., HA-CVB3_2C(322-329) and HA-GN1_2C(322-329)) are added to the plate for capture by the plate-bound recombinant Trim7 protein. Recombinant human RAC01, MSK1 and / or STING protein is added to the plate with or without the peptides disclosed herein (e.g., HA-CVB3_2C(322-329) and / or HA-GN1_2C (322-329)). The binding is then detected using anti-RAC01 antibody, and / or anti-MSK1 antibody and / or anti-STING antibody in combination with a SULFO-TAG conjugated secondary antibody. It is expected that Trim7 will exhibit binding to RAC01, MSK1 and / or STING protein in the absence of the peptides disclosed herein (See FIG. 1A to FIG. 1E). It is anticipated that Trim7 will exhibit reduced binding to RAC01, MSK1 and / or STING protein when the detection is performed in the presence the peptides disclosed herein. These results will demonstrate, inter alia, that the peptides disclosed herein disrupt the binding of recombinant human Trim7 protein to RAC01, MSK1 and / or STING protein. Accordingly, the compounds of formula (I) are inhibitors of Trim7, which are useful in the methods disclosed herein. Example 7: TRIM7 interaction with SMIs of the disclosure TRIM7 is most described in viral biology, where it ubiquitinates viral proteins (e.g., CVB3_2BC, EV71, and SARS-CoV2) and targets them for degradation (FIG. 6A). The crystal structure of the c-term Pry Spry domain of TRIM7 was recently solved, identifying the key pocket where viral binding could occur (FIG. 6B). The crystal structure of TRIM7 with viral peptide was solved and identified a key cysteine in the binding pocket that could be exploited for covalent binding (FIG. 6C). Importantly, the c-term amino acids of viral CVB3_2C were shown to specifically interact in this pocket, and this amino acid motif is conserved with the native proteins GN1 and RAC0-1. These structural learnings partially informed the small molecule inhibition of TRIM7. Recombinant proteins were generated to facilitate small molecule inhibitor (SMI) development and to verify binding / functional activity. TRIM7 interactions with RAC0-1, STING, MAVS, and CVB3_2C (WT but not mutant) were confirmed (FIG. 7). Using these findings, various compounds of the disclosure have been developed, screened through a series of binding / activity assays, and prioritized for further chemical modification (FIG. 8). The disruption of the CVB3 peptide from TRIM7 using SMIs of the disclosure was studied using fluorescence polarization (FP) (FIG. 9). The data demonstrates SMI-1 outperforms the native peptide's ability to disrupt fluorescently labelled CVB3 from TRIM7, but SMI-2 has lower activity than the viral control peptide. FIGS 10A-10C and Table 1 confirm that TRIM7 SMIs specifically bind C501 in the PrySpry domain. Mass spectrometry confirmed SMI binding of peptides SMI-1 and SMI-2 (shown below) to TRIM7 (FIG. 10A), the kinetics of binding (FIG. 10B), and specificity to the target cysteine in the TRIM7_PrySpry binding pocket (FIG. 10C). Table 1 provides binding data for the control peptides and several compounds of the disclosure. Binding was assessed qualitatively, with a score of*, **, ***, or**** based on whether the correct SMI mass was detected following incubation with TRIM7_PrySpry (Full Scan), and whether an interaction was confirmed at the intended C501 in the binding pocket (peptide mapping). SMI-1                     SMI-2 Legend: Scores of * or ** indicate some binding was detected however assay requires further optimization. Scores of *** or **** jnc|jcate confidence binding. ND indicates that the compound has not been tested. Table 1. Binding data to the PrySpry domain for compounds of the disclosure SMI Binding by Mass Spec Full Scan to TRIM7 PrySpry Binding at 0501 in TRIM7 PrySpry through Peptide Mapping SMI-1 **** **** SMI-2 *** *** SMI-8 *** *** SMI-3 ** ND In summary, various compounds of the disclosure have been synthesized and prioritized through a series of binding / activity assays. The specific binding was confirmed specific binding through BLI, fluorescent polarization, and mass spec analysis. The functional activity was validated through the disruption of target ubiquitination and stabilization. TRIM7 inhibition in CT26 / AR was found to result in decreased proliferation and increased apoptosis. The TRIM7 SMIs were also found to disrupt proliferation of TRIM7-expressing KRAS mutant human cancer cell lines and the activity of TRIM7 SMI is improved in combination with KRAS inhibition. Taken together, these results demonstrate that TRIM7 may be a driver of ICB acquired resistance and its inhibition alone or in combination with KRAS pathway inhibition, may be a therapeutic approach to treat ICB resistance and restore patient sensitivity to immune checkpoint therapy. Example 8: In vivo anti-tumor activity of a compound of formula (I) in Combination with a kras Inhibitor The efficacy of a compound of formula (I) is evaluated in combination with a kras inhibitor. Briefly, BALB / C mice are inoculated with 500,000 murine colon carcinoma CT26 cells on the rear flank. When average tumor volume reached 80-100 mm3 (indicating day 0), mice, the mice are randomly distributed in four following treatment groups. The groups of mice are administered (1) vehicle only control, (2) a compound of formula (I) alone, (3) kras inhibitor alone, or (4) a combination of a compound of formula (I) and a kras inhibitor. The administration is performed on days on days 0, 3, 6, 9, 12, and 15. Tumors are measured with electronic calipers on every day and plotted using the GraphPad Prism software. The tumor growth for each treatment group is assessed by plotting tumor growth curves of individual mice, average tumor growth curves for treatment groups, average tumor sizes on an illustrative day, and / or Kaplan-Meier plots. The results are expected to demonstrate, inter alia, that the combination of a compound of formula (I) and a kras inhibitor has greater anti-tumor activity compared to either single treatment. Example 9: In vivo anti-tumor activity of a compound of formula (I) in Combination with a braf Inhibitor The efficacy of a compound of formula (I) is evaluated in combination with a braf inhibitor. Briefly, BALB / C mice are inoculated with 500,000 murine colon carcinoma CT26 cells on the rear flank. When average tumor volume reached 80-100 mm3 (indicating day 0), mice, the mice are randomly distributed in four following treatment groups. The groups of mice are administered (1) vehicle only control, (2) a compound of formula (I) alone, (3) braf inhibitor alone, or (4) a combination of a compound of formula (I) and a braf inhibitor. The administration is performed on days on days 0, 3, 6, 9, 12, and 15. Tumors are measured with electronic calipers on every day and plotted using the GraphPad Prism software. The tumor growth for each treatment group is assessed by plotting tumor growth curves of individual mice, average tumor growth curves for treatment groups, average tumor sizes on an illustrative day, and / or Kaplan-Meier plots. The results are expected to demonstrate, inter alia, that the combination of a compound of formula (I) and a braf inhibitor has greater anti-tumor activity compared to either single treatment. Example 10: in vivo anti-tumor activity of a compound of formula (I) in Combination with a MEK Inhibitor The efficacy of a compound of formula (I) is evaluated in combination with a MEK inhibitor. Briefly, BALB / C mice are inoculated with 500,000 murine colon carcinoma CT26 cells on the rear flank. When average tumor volume reached 80-100 mm3 (indicating day 0), mice, the mice are randomly distributed in four following treatment groups. The groups of mice are administered (1) vehicle only control, (2) a compound of formula (I) alone, (3) MEK inhibitor alone, or (4) a combination of a compound of formula (I) and a MEK inhibitor. The administration is performed on days on days 0, 3, 6, 9, 12, and 15. Tumors are measured with electronic calipers on every day and plotted using the GraphPad Prism software. The tumor growth for each treatment group is assessed by plotting tumor growth curves of individual mice, average tumor growth curves for treatment groups, average tumor sizes on an illustrative day, and / or Kaplan-Meier plots. The results are expected to demonstrate, inter alia, that the combination of a compound of formula (I) and a MEK inhibitor has greater anti-tumor activity compared to either single treatment. Example 11: / C50 data of compounds of the disclosure This Example provides data showing IC50 values of compounds of the disclosure from a TRIM / fluorescence polarization (FP) binding assay. A TRIM7 fluorescence polarization (FP) binding assay was performed on compounds of the disclosure. The assay was performed using the far C-terminal 9 amino acids (GATLEALFQ (SEQ ID NO: 1)) of a fluorescently labeled viral peptide (CVB3) previously shown to interact with the same TRIM7-PrySpry(324-511) domain (Ru, Y. et al., Proc. Natl. Acad. Sci. U.S.A., 2022, 119(3): e2203218119), which was incubated for 22 hours with His-TRIM7-PrySpry(324-511). An unlabeled version of the same peptide, a shorter version of that peptide (LFQ only), or the small molecule inhibitors (SMIs) were added to compete with the binding of the fluorescently labeled peptide to the same docking pocket. The loss of fluorescent signal as the labeled peptide is competed off was quantified. The results are shown in the table below, where the IC50 is indicated as follows: Key: +++ = IC50 < 15 piM ++= 15 pM < IC50 < 100 piM + = IC50 > 100 pM N / A = Compound not yet tested Compound Structure IC50 (30 mins) IC50 (1.5 hrs) IC50 (4 hrs) IC50 (22 hrs) SMI-1 0 X H      I II H H,N ...,0 A 0 f"" it A. .X OH ■' V N K ’ >V +4-4- +++ +++ +++ SMI-2 Q । □f O ;>—x    / -Q X        2JX ;    \\ / ’ / IZ .......( N / A + + ++ SMI-3 O \\       / / «2»                 ' \ \ y-o b \ / ......f zx op N / A ++ +++ +++ SMI-4 )     1 H > H-?N x ....,0 ' M 0     f""" n          f Nx A.,A .OH ""        N' V 5 •<           6 TS I ++ ++ +++ ++ SMI-5 c k 0:::::(      \....... h2nx,,,o M   0   f ’ H     ,5      1 N.           .OH - H >1 \.....   0 ++ ++ ++ ++ SMI-6 O.      Z b x"       2 ox / \ / ox. 4- 4- 4- 4- ■} M Si 0 k.....,. o SMI-7 ° £ r N" ' H ( ■,------- „M-yo \\   z) IZ        X '".........           '■■>•>>... 'x Q™,- /     \.......( b b X N / A 4- 4- 4- SMI-8 0   | 0 H ( KN. ...0 .                               *■      V'',''' ? / X Ax ..-. OH r      n '  v 3   •< H   6 yA N / A 4- ++ 4-4-4- SMI-9 0 r     0 f H 6 \ H 6 N / A 4- 4- 4- SMI-10 / V““O ZZZ. / \ }....... "'ZT > ...... \ \ zz '........ '•— o    a ++ 4-4-4- ++ N / A SMI-11 X a    o 'y......x Wo X       (     ........ £:     xx / o ■■■■■-,     ^. / ' .......(   >-o \ / XX Op +++ +++ +++ N / A SMI-12 0         o V-N 1 H        ■ ++ ++ N / A N / A SMI-13 X p oW    « ■■.                X Wo  o XX OW / \ / . / X J- , / oz' - ' ++ ++ N / A N / A SMI-14 f H X.....W N- V J H 0 / \                                        $ \                                      $ ++ ++ N / A N / A SMI-15 । f"V ? , / W w x VN 'v^qh ><J H 6 . / “    0-¾ ++ ++ N / A N / A SMI-16 QA .......k Any \ Vy* ......Z     o Z     X ++4- +++ N / A N / A SMI-17 V                                 fl 1 L!X X V / A n Ar a oh \ J H A ( / Ah +++ +++ N / A N / A SMI-18 A^N H 9 !h 9 o y 6 O^NH^ +++ +++ N / A N / A SMI-19 X    X o    z- °A.„ / A / \zz Ay y.Q z— +++ +++ N / A N / A SMI-20 V o < A o ' B J d I! O i I x +++ +++ N / A N / A SMI-21 A xx -rS-o 'TZ o ,rw >.....' —z    o X    X +++ +++ N / A N / A SMI-22 S A X Xx ' YTTY 0       ° A t / Ah. ++ +++ N / A N / A SMI-23 X     X O    Z A O= / Q X~\ ++ ++ N / A N / A SMI-24 \      c,   °           ° Yyx    H    j|    I H a \^¼AA)H 6 k 6 a f > O^NHi ++ ++ N / A N / A SMI-25 n O (       0 LX A X JI A' K Y V Y--^        O + ++ N / A N / A SMI-26 r    x 0-7°   - f / —1 <z xx o, I 4- ++ N / A N / A SMI-27 ( ? rif p L xL       / N     Xr 0 H 61 4- ++ N / A N / A SMI-28 >=o / — 7X\\ ) o A-.>y *—y y— / ^=0 z    o ? \ 4- ++ N / A N / A SMI-29 O^NH; 4-4-4- 4-4-4- N / A N / A SMI-30 m x i ,Oh * i ++ ++ N / A N / A SMI-31 c ( r"        / z    O >~\ / -° O X- / ZI °5"v. . pX2\ _r i] ++ ++ N / A N / A SMI-32 , J J H II J H H A + ++ N / A N / A SMI-33 I iX XaY Y x nr y CT-NH; 4- + N / A N / A SMI-34 Q5 n° Q , ( ; ____ / \ ......Z O X X +++ +++ N / A N / A SMI-35 / X \ ,p yy -Xtvrx, \ ) H II i 0 1 CrAlH, +++ +++ N / A N / A SMI-36 X      T* O    Z O=T r..... r"' x° C h X2\™. p=o M ZI ex k +++ +++ N / A N / A SMI-37 YXa Y q- nc y O^NH, +++ +++ N / A N / A INCORPORATION BY REFERENCE All patents and publications referenced herein are hereby incorporated by reference in their entireties. The publications discussed herein are provided solely for their disclosure prior to the filing date of the present 5 application. Nothing herein is to be construed as an admission that the present disclosure is not entitled to antedate such publication by virtue of prior disclosure. As used herein, all headings are simply for organization and are not intended to limit the disclosure in any manner. The content of any individual section may be equally applicable to all sections. EQUIVALENTS 10 While the disclosure has been disclosed in connection with specific embodiments thereof, it will be understood that it is capable of further modifications and this application is intended to cover any variations, uses, or adaptations of the disclosure following, in general, the principles of the disclosure and including such departures from the present disclosure as come within known or customary practice within the art to which the disclosure pertains and as may be applied to the essential features hereinbefore set forth and as follows in the scope of the appended claims. Those skilled in the art will recognize, or be able to ascertain, using no more than routine experimentation, numerous equivalents to the specific embodiments disclosed specifically herein. Such equivalents are intended to be encompassed in the scope of the following claims.

Claims

1. A compound of the formula (I):L1-(([Aaa]w)n-[Aaa]x-[Aaa]y-[Aaa]z-Ter)-L2whereinL1 is present or absent, and if present, is selected from a chemical group, a carrier protein, and a tag, the chemical group is optionally selected from acryloyl, amino, alkyl, acyl group, a glycosyl moiety, and a polymer;L2 is absent or present, and if present, is selected from a chemical group, a carrier protein, and a tag, the chemical group is optionally selected from acryloyl, amino, alkyl, acyl group, a glycosyl moiety, and a polymer;each [Aaa]w is independently selected from an amino acid;n = 0-20;[Aaa]xis absent or is an amino acid;[Aaa]yis an amino acid or is absent;[Aaa]zis an aromatic or a hydrophobic amino acid; andTer is Gin or Asn.

2. The compound of claim 1, wherein Ter is Gin.

3. The compound of claim 1 or claim 2, wherein [Aaa]z is an aromatic amino acid selected from Phe, 3-methyl-Phe, Tyr, Trp, wherein the nitrogen of the aromatic amino acid is optionally substituted with an alkyl group, optionally a methyl group.

4. The compound of claim 3, wherein [Aaa]z is Phe or 3-methyl-Phe.

5. The compound of claim 1 or claim 2, wherein [Aaa]z is a hydrophobic amino acid selected from Leu, Vai, He,Ala, 3-(pyridin-4-yl)-Ala, and 3-(pyridin-3-yl)-Ala.

6. The compound of claim 5, wherein [Aaa]z is Leu, 3-(pyridin-4-yl)-Ala, or 3-(pyridin-3-yl)-AIa.

7. The compound of claim 1 or claim 2, wherein [Aaa]z is Met.

8. The compound of any one of claims 1 to 7, wherein [Aaa]y and / or [Aaa]x is present and, if present, each isindependently a natural amino acid.

9. The compound of claim 8, wherein [Aaa]y is present and is a nonpolar amino acid, an aromatic amino acid or a polar amino acid.

10. The compound of claim 8 or 9, wherein [Aaa]y is a nonpolar amino acid selected from Vai, Gly, Ala, Leu, Met, Trp, Phe, lie, Pro or an analogue thereof, optionally wherein Pro analogue is selected from (R)-p-Pro and (S)-p-Pro, optionally wherein Ala analogue is 3-(4-pyridyl)-L-alanine, or optionally wherein Pro is (R)-Pro or (S)-Pro, wherein the alpha carbon of the Pro is optionally substituted with an alkyl group, optionally a methyl group (e.g. a-methyl-L-proline), optionally wherein the alpha carbon of the Gly is substituted with an alkyl or cycloalkyl group, optionally a cyclopropyl group (e.g. o-cyclopropane-Gly), optionally wherein the beta carbon of the Ala is substituted with a aryl or heteroaryl, optionally a pyridine group.

11. The compound of claim 10, wherein [Aaa]yis selected from Leu, Trp, Pro, (R)-|3-Pro, (S)-p-Pro, (R)-Pro, (S)-Pro, 3-(4-pyridyl)-L-alanine, and o-cyclopropane-Gly, wherein the alpha carbon of the Pro is optionally substituted with an alkyl group, optionally a methyl group (e.g. a-methyl-L-proline).

12. The compound of claim 8 or 9, wherein [Aaa]yis a polar amino acid selected from Ser, Thr, Gin, and Asn.

13. The compound of claim 9, wherein the polar amino acid is a charged amino acid selected from Lys, Arg, His,Glu, and Asp.

14. The compound of claim 8 or 9, wherein [Aaa]yis an aromatic amino acid selected from Tyr, Trp, and Phe.

15. The compound of claim 14, wherein [Aaa]y is Tyr.

16. The compound of claim 8, wherein [Aaa]yis a hydrophobic amino acid selected from Vai, Leu, and lie.

17. The compound of claim 16, wherein [Aaa]yis Leu.

18. The compound of any one of claims 8-17, wherein [Aaa]xis present and is a nonpolar amino acid, an aromatic amino acid, or a polar amino acid.

19. The compound of claim 18, wherein [Aaa]x is a nonpolar amino acid selected from Vai, Gly, Ala, Leu, Met,Trp, Phe, lie, and Pro or an analogue of any one thereof, optionally wherein [Aaa]xis Ala and / or optionally wherein Prois (R)-|3-Pro or (S)-p-Pro.

20. The compound of claim 19, wherein [Aaa]xis an aromatic amino acid selected from Tyr, Trp, and Phe.

21. The compound of claim 20, wherein [Aaa]x is Phe.

22. The compound of claim 18, wherein [Aaa]x is a polar amino acid selected from Ser, Thr, Gin, and Asn,optionally wherein [Aaa]x is Thr.

23. The compound of any one of claims 1-22, wherein L1 is present and is acryloyl or an acyl group, optionally wherein the acyl group is CH3-CH2-C(O)-, CH3-C(O)-, or CH3-C=C-C(O)-.

24. The compound of any one of claims 1-23, wherein L2 is present and is amino or -OCH3.

25. The compound of any one of claims 1-24, wherein the compound comprises at least one, or at least two, or at least three, or at least 4, or at least 5, or at least 6, or at least 7, or at least 8, or at least 9, or at least 10, or at least 15 [Aaa]w, or wherein n is 0 and [Aaa]wis absent.

26. The compound of claim 25, wherein each [Aaa]w is independently a natural amino acid, optionally independently selected from a nonpolar amino acid, an aromatic amino acid, or a polar amino acid.

27. The compound of any one of claims 1-26, wherein one or more of [Aaa]w, [Aaa]x, and [Aaa]y are present and are each independently naturally modified amino acids, optionally one or more of 4-hydroxyproline, 5-hydroxylysine, and glycosylated amino acids.

28. The compound of any one of claims 1-27, wherein L1 and / or L2 is or comprises a carrier protein selected from Fc domain, albumin, transferrin, or elastin-like protein, Keyhole Limpet Hemocyanin (KLH), ovalbulin, or a variant thereof.

29. The compound of claim 28, wherein the carrier protein comprises a Fc domain selected from an IgG Fc domain, an IgA Fc domain, an IgM Fc domain, an IgE Fc domain, and an IgD Fc domain.

30. The compound of claim 29, wherein the carrier protein comprises an IgG Fc domain and the IgG Fc domain is selected from an IgG 1 Fc domain, an lgG2 Fc domain, an lgG3 Fc domain, and an lgG4 Fc domain.

31. The compound of claim 29, wherein the carrier protein comprises an IgA Fc domain and the IgA Fc domain is selected from an lgA1 Fc domain and an lgA2 Fc domain.

32. The compound of any one of claims 28-31, wherein L2 is absent, wherein the compound has the formula: carrier protein-(([Aaa]w)n-[Aaa]x-[Aaa]y-[Aaa]z-Ter).

33. The compound of any one of claims 28-31, wherein L1 is absent, wherein the compound has the formula: (([Aaa]w)n-[Aaa]x-[Aaa]y-[Aaa]z-Ter)-carrier protein.

34. The compound of any one of claims 28-33, wherein the carrier protein is linked to (([Aaa]w)n-[Aaa]x-[Aaa]y-[Aaa]z-Ter) via a peptide linker.

35. The compound of claim 34, wherein the peptide linker is rigid or flexible.

36. The compound of any one of claims 1-35, wherein L1 and / or L2 comprises or further comprises a tag selectedfrom hexahistidine tag, FLAG tag, Strep II tag, streptavidin-binding peptide (SBP) tag, calmodulin-binding peptide (CBP), glutathione S-transferase (GST), maltose-binding protein (MBP), S-tag, HA tag, and c-Myc tag.

37. The compound of any one of claims 1-35, wherein L1 and / or L2 comprises or further comprises a glycosyl moiety.

38. The compound of claim 37, wherein the glycosyl moiety is an N-linked glycosyl moiety.

39. The compound of claim 37, wherein the glycosyl moiety is an O-linked glycosyl moiety.

40. The compound of any one of claims 37-39, wherein the compound comprises one or more N-linkedglycosylation consensus sites and / or O-linked glycosylation consensus sites.

41. The compound of claim 40, wherein the one or more N-linked glycosylation consensus sites and / or O-linked glycosylation consensus sites are present in ([Aaa]w)n-[Aaa]x-[Aaa]y-[Aaa]z-Ter), the carrier protein, or the tag.

42. The compound of any one of claims 1-41, wherein the compound is biosynthesized as a single polypeptide chain.

43. The compound of any one of claims 1-42, wherein the compound is biosynthesized from a single open reading frame.

44. The compound of any one of claims 1-43, wherein the compound is prepared using an expression system.

45. The compound of claim 44, wherein the expression system is selected from bacterial, yeast, invertebrate (e.g.,an insect cell), vertebrate (e.g., a mammalian cell), and plant expression system.

46. The compound of any one of claims 1-45, wherein one or more of [Aaa]w, [Aaa]x and [Aaa]y are present and are independently selected from non-natural amino acids, optionally D-amino acids (Daa) or non-natural amino acids comprising N-methylation (Nm), Ca-methylation (Cm), amino isobutyric acids (Aib), ^(CEbNH) reduced amide bonds (Rd), and peptoids (Pp).

47. The compound of any one of claims 1-46, wherein L1 and / or L2 comprises or further comprises an alkyl or acyl group that is conjugated to the compound, optionally wherein the acyl group is CH3-CH2-C(O)-, CH3-C(0)-, or CH3-C=C-C(O)-.

48. The compound of claim 47, wherein L1 and / or L2 comprises an acyl group, optionally wherein the acyl group is CH3-CH2-C(O)-, CH3-C(O)-, or CH3-C=C-C(O)-.

49. The compound of any claim 48, wherein the acyl group is an acetyl group.

50. The compound of any one of claims 1-49, wherein L1 and / or L2 comprises or further comprises a polymer,which is optionally selected from poly(alkylene oxide), further optionally polyethylene glycol (PEG), poly(N-vinylpyrrolidone), poly(vinyl alcohol), poly(glycerol), poly(zwitterions), poly(carbonates), polyoxazoline, poly(acryloylmorpholine), poly(oxazolines), poly(saccharides), and a combination thereof.

51. The compound of claim 50, wherein the polymer is polyethylene glycol (PEG).

52. The compound of claim 51, wherein one or more amino acids present in the present in ([Aaa]w)n-[Aaa]x-[Aaa]y-[Aaa]z-Ter), the carrier protein, or the tag are PEGylated, optionally wherein one or more PEGylated amino acids comprises Lys and PEGylation is conducted via amine conjugation.

53. The compound of claim 52, wherein one or more PEGylated amino acids comprises Gin and PEGylation is conducted via transglutaminase (TGase) mediated enzymatic conjugation.

54. The compound of any one of claims 52 or 53, wherein one or more PEGylated amino acids comprises Cys and PEGylation is conducted via thiol conjugation.

55. The compound of any one of claims 1-54, wherein the compound of formula (I) is selected from L1 -Phe-GIn, L1-Leu-Phe-Gln, L1-Leu-Phe-Gln-L2, L1-Leu-3-methyl-Phe-Gln, L1-(R)-|3-Pro-Phe-Gln, or L1-(S)-|3-Pro-Phe-Gln, optionally wherein L1 is an acyl group or acryloyl and optionally wherein L2 is amino.

56. The compound of claim 1, wherein the compound is a compound of formula (II):O R1a p1b O x^^ o kO^NR4aR4bFormula (II)a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein in formula (II):R1a and R1b are at each occurrence independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl;R2 is selected from hydrogen, unsubstituted or substituted alkyl, and unsubstituted or substituted alkylaryl;X is selected from -CH=CH2,Y is selected from -0R3a, and -NR3bR3c;R3a, R3b and R3c are at each occurrence independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkylaryl, and unsubstituted or substituted aryl; optionally wherein R3b and R3c are joined to form an optionally substituted cycloalkyl;R4a and R4b are at each occurrence independently selected from hydrogen, unsubstituted or substituted alkyl, and unsubstituted or substituted alkylaryl, optionally wherein R4a and R4b are joined to form an optionally substituted cycloalkyl;R5 is selected from unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted aryl, and unsubstituted or substituted alkylaryl;R6 is selected from hydrogen, unsubstituted or substituted alkyl, and unsubstituted or substituted alkylaryl;R7 is selected from unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted aryl, and unsubstituted or substituted alkylaryl;R8a and R8b are at each occurrence independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl, optionally wherein R8a and R8b are joined to form an optionally substituted cycloalkyl;R9 is selected from unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted aryl, and unsubstituted or substituted alkylaryl; andR10 is selected from hydrogen, unsubstituted or substituted alkyl, and unsubstituted or substituted alkylaryl.

57. The compound of claim 56, wherein Y is selected from -OH, OCH3, NH2, NHMe, and NMe2.

58. The compound of claim 56 or claim 57, wherein R1a is hydrogen and R1b is selected from:"O=\  O^-\\ / /         \v y'pH j — k , and ;wherein R11 is selected from hydrogen, unsubstituted or substituted alkyl, and unsubstituted or substituted alkylaryl.

59. The compound of any one of claims 56-58, wherein R11 is methyl.

60. The compound of any one of claims 56-59, wherein R1a and R1b are at each occurrence independently selected from:hydrogen,61. The compound of any one of claims 56-60, wherein R4a and R4b are at each occurrence independently selected from hydrogen, methyl, isopropyl, and isobutyl.

62. The compound of any one of claims 56-61, wherein R2 is selected from hydrogen, methyl, isopropyl, and isobutyl; optionally wherein R2 is selected from hydrogen and methyl.

63. The compound of any one of claims 56-62, wherein R5 is selected from -CH=CH2, -CH2-CH3, and -C=CCH3.

64. The compound of any one of claims 56-63, wherein R6 is selected from hydrogen and methyl.

65. The compound of any one of claims 56-64, wherein R7 is selected from -CH3, -CH=CH2, -CH2-CH3, and -C=CCH3.

66. The compound of any one of claims 56-65, wherein R8a is hydrogen, and R8b is selected from hydrogen, methyl, isopropyl, and isobutyl.

67. The compound of any one of claims 56-66, wherein R8a and R8b are joined to form an optionally substituted cycloalkyl; optionally R8a and R8b are joined to form cyclopropyl.

68. The compound of any one of claims 56-67, wherein R9 is selected from -CH=CH2, -CH2-CH3, and -C=CCH3.

69. The compound of any one of claims 56-68, wherein R10 is selected from hydrogen and methyl.

70. The compound of claim 56, wherein the compound is a compound of formula (Ila):O   R1b u   OII       I       H       IIA A .n. Ax n y A yO^NR4aR4bFormula (Ila).

71. The compound of claim 56, wherein the compound is a compound of formula (lib):O R1b u OR2 0 h O^NR4aR4bFormula (lib).

72. The compound of claim 56, wherein the compound is a compound of formula (lie):Formula (lie).

73. The compound of claim 56, wherein the compound is a compound of formula (Illa):Formula (Illa).

74. The compound of claim 56, wherein the compound is a compound of formula (lllb):Formula (lllb).

75. The compound of any one of claims 70-74, wherein R1b is selected from:

76. The compound of any one of claims 70-75, wherein R2 is selected from hydrogen and methyl.

78. The compound of any one of claims 70-77, wherein R4a and R4b are at each occurrence independently selected from hydrogen and methyl.

79. The compound of any one of claims 70-78, wherein R8b is isobutyl.

80. The compound of any one of claims 70-79, wherein R7 is selected from -CH3, -CH=CH2, -CH2-CH3, and -C=CCH3.

81. The compound of any one of claims 70-80, wherein R5 is selected from -CH=CH2, -CH2-CH3, and -C=CCH3.

82. The compound of any one of claims 70-81, wherein R6 is selected from hydrogen, and methyl.

83. The compound of any one of claims 70-82, wherein R9 is selected from -CH=CH2, -CH2-CH3, and -C=CCH3.

84. The compound of any one of claims 70-83, wherein R10 is selected from hydrogen, and methyl.

85. The compound of any one of claims 1-84, wherein the compound of formula (I) is a compound of any one of formulas SMI-1 to SMI-40:Formula No. Structure SMI-1 X O.     O / --,    7""O / --■■■ X     XX f O-< .......<   7-0 \ / ^x 0—(SMI-2 Hp, ..,0 9 1H ° I H $    .-. H $ SMI-3 o         o !     H      4; H 6 > SMI-4 o. o >......-, Wo ,-........, -p                       / / ■    \\ 0¾  )-¾ \ / / — / x      / 0¾ SMI-5 ° r h t .„,0 p ? f1 N. ,k A, OH f        N' >f 3    -<x       O SMI-6 0    *' Jt ,1 'N' > H i H2N s ^0 u  0   f n      is      f .N. Ak.A ,NH-; f V N >f x ?■ '■••'■••.SMI-7 o - N A H * HoN ..0 Z ? r" H * $ _ o •':          V'- / /         f SMI-8 H I A'N > !■ H * H2N ^... 0 "V 0 M                •. .N.       ..---. OH ......- • '>f- ' H x x 0 v......S SMI-9 C ' N ' ' H "h  0   f" n    o    f N. A,., A NHo N -?f 5 A $ --'A SMI-10 < 2 Z "n H H^N O N. .A, A .OH N V 0  \    O ..-‘''J SMI-11 xz o™ y...... ±x / ..    .....Vo OA 4 0-7     .....-<( o    o XSMI-17 v a JO O^NH SMI-18 U 0 x-< ? N"V Ah 0 A / d \ ( / \K; SMI-19 \\ A A XN O T f H -v 0 Q A X NH 1 z-0 0 0 0 SMI-20 b'S 1 H A. Q Aon 'I \J Nn? c / s \ / SMI-21 { »       Vz 'N^Sr 6 < J JII A OH O^XNHSMI-22 am u 0          O o < / 6 < 1    J Cr SMI-23 V o VV k A Im of V v - SMI-24 / V zi / ’’X □ ao >J A 2!       0 A SMI-25 jo jCa O f As 0 / AAaM-oh V H A i SMI-26 X    X O       s:-— q= / '° 2!T Q=V o   / a vJ / SMI-32 Co 0         o f * H H f - rf / ry" o SMI-33 । o o             o SMI-34 cyk IZ kA ZI / /     / O / '.■; / \— / z    a SMI-35 „o ^IX-Ut / Ss'               oh VJ H A O^NH, SMI-36 o o f X 0 SMI-37 n /    or       ^oh u h n O^'NH,86. The compound of any one of claims 1 to 54, wherein the compound comprises an amino acid sequence of any one of SEQ ID NOs: 1-15, or a variant thereof having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid mutations with respect to an amino acid sequence selected from SEQ ID NOs: 1 to 15.

87. An isolated polynucleotide encoding a compound of any one of claims 1-43 or 86.

88. The isolated polynucleotide of claim 87, wherein the isolated polynucleotide is or comprises DNA or RNA.

89. The isolated polynucleotide of claim 88, wherein the isolated polynucleotide is DNA.

90. The isolated polynucleotide of claim 87, wherein the nucleic acid is RNA.

91. The isolated polynucleotide of claim 90, wherein the RNA is an mRNA, optionally wherein the mRNA a modified mRNA (mmRNA).

92. A vector comprising the isolated polynucleotide of any one of claims 87 to 90.

93. A host cell comprising the isolated polynucleotide of any one of claims 87 to 91 or the vector of claim 92.

94. A pharmaceutical composition comprising a compound of any one of claims 1-86, or the isolated polynucleotide of any one of claims 87 to 91, or the vector of claim 92, or the host cell of claim 93.

95. A pharmaceutical composition comprising a pharmacologically acceptable carrier and:a polypeptide comprising an amino acid sequence that is at least 90%, or at least 95%, or at least 97%, or at least 98% identical to the amino acid sequence of SEQ ID NO 1 or 2; ora peptide comprising an amino acid sequence of any one of SEQ ID NOs: 3-8 or a variant having about 1, 2, 3, 4, 5 or more amino acid mutations with respect to an amino acid sequence selected from SEQ ID NOs: 3 to 8; ora peptide comprising an amino acid sequence of any one of SEQ ID NOs: 9-12 or a variant having about 1, 2, 3, 4, 5 or more amino acid mutations with respect to an amino acid sequence selected from SEQ ID NOs: 9 to 12; ora peptide comprising an amino acid sequence of SEQ ID NO: 15 or a variant having about 1, 2 more amino acid mutations with respect to an amino acid sequence selected from SEQ ID NO: 15.

96. A method for treating a cancer, an infectious disease, an inflammatory disease in a subject in need thereof, the method comprising administering to the subject the pharmaceutical composition of claim 94 or claim 95.

97. The method of claim 96, wherein the cancer is selected from a basal cell carcinoma, biliary tract cancer; bladder cancer; bone cancer; brain and central nervous system cancer; breast cancer; cancer of the peritoneum; cervical cancer; choriocarcinoma; colon and rectum cancer; connective tissue cancer; cancer of the digestive system; endometrial cancer; esophageal cancer; eye cancer; cancer of the head and neck; gastric cancer (including gastrointestinal cancer); glioblastoma; hepatic carcinoma; hepatoma; intra-epithelial neoplasm; kidney or renal cancer; larynx cancer; leukemia; liver cancer; lung cancer (e.g., small-cell lung cancer, non-small cell lung cancer, adenocarcinoma of the lung, and squamous carcinoma of the lung); melanoma; myeloma; neuroblastoma; oral cavity cancer (lip, tongue, mouth, and pharynx); ovarian cancer; pancreatic cancer; prostate cancer; retinoblastoma; rhabdomyosarcoma; rectal cancer; cancer of the respiratory system; salivary gland carcinoma; sarcoma; skin cancer; squamous cell cancer; stomach cancer; testicular cancer; thyroid cancer; uterine or endometrial cancer; cancer of the urinary system; vulval cancer; lymphoma including Hodgkin's and non-Hodgkin's lymphoma, as well as B-cell lymphoma (including low grade / follicular non-Hodgkin's lymphoma (NHL); small lymphocytic (SL) NHL; intermediate grade / follicular NHL; intermediate grade diffuse NHL; high grade immunoblastic NHL; high grade lymphoblastic NHL; high grade small non-cleaved cell NHL; bulky disease NHL; mantle cell lymphoma; AIDS-related lymphoma; and Waldenstrom's Macroglobulinemia; chronic lymphocytic leukemia (CLL); acute lymphoblastic leukemia (ALL); Hairycell leukemia; chronic myeloblastic leukemia; as well as other carcinomas and sarcomas; and post-transplant lymphoproliferative disorder (PTLD), as well as abnormal vascular proliferation associated with phakomatoses, edema (such as that associated with brain tumors), and Meigs' syndrome.

98. The method of claim 96 or claim 97, wherein the cancer is a hematologic cancer selected from the group consisting of chronic lymphocytic leukemia (CLL), acute leukemias, acute lymphoid leukemia (ALL), B-cell acute lymphoid leukemia (B-ALL), T-cell acute lymphoid leukemia (T-ALL), chronic myelogenous leukemia (CML), B cell prolymphocytic leukemia, blastic plasmacytoid dendritic cell neoplasm, Burkitt's lymphoma, diffuse large B cell lymphoma, follicular lymphoma, hairy cell leukemia, small cell- or a large cell-follicular lymphoma, malignant lymphoproliferative conditions, MALT lymphoma, mantle cell lymphoma, marginal zone lymphoma, multiple myeloma, myelodysplasia and myelodysplastic syndrome, non-Hodgkin’s lymphoma, Hodgkin's lymphoma, plasmablastic lymphoma, plasmacytoid dendritic cell neoplasm, Waldenstrom macroglobulinemia, and pre-leukemia, or a combination thereof.

99. The method of any one of claims 96 to 98, wherein the cancer is resistant to an anti-checkpoint agent.

100. The method of claim 99, wherein the anti-checkpoint agent is an antibody, optionally selected from an anti-PD-1, anti-PD-LI, anti-PD-L2, and anti-CTLA antibody.

101. The method of claim 100, wherein the antibody is selected from nivolumab (OPDIVO), pembrolizumab (KEYTRUDA), pidilizumab (CT-011, CURE TECH), MK-3475 (MERCK), BMS 936559, MPDL328OA (ROCHE), Cemiplimab (LIBTAYO), Atezolizumab (TECENTRIQ), Avelumab (BAVENCIO), and Durvalumab (imfinzi).

102. The method of claim 96, wherein the infectious disease is a viral infection.

103. The method of claim 102, wherein the viral infection is caused by a virus selected from papillomavirus, herpes simplex virus (HSV), human immunodeficiency virus (HIV), hepatitis virus, Zika virus, Yellow Fever Virus, West Nile virus, Dengue virus, Japanese Encephalitis Virus, St. Louis Encephalitis Virus, Hepatitis C Virus, poliovirus, rhinovirus, enterovirus, coxsackievirus, influenza virus, lentivirus, respiratory syncytial virus, a human parainfluenza virus, rubulavirus (e.g, mumps virus), measles virus, human metapneumovirus, hantavirus, rotavirus, norovirus, and SARS virus (e.g, SARS-CoV-2).

104. The method of claim 96, wherein the inflammatory disease is an autoimmune disease or condition, selected from multiple sclerosis, diabetes mellitus, lupus, celiac disease, Crohn's disease, ulcerative colitis, Guillain-Barre syndrome, scleroderms, Goodpasture's syndrome, Wegener's granulomatosis, autoimmune epilepsy, Rasmussen's encephalitis, Primary biliary sclerosis, Sclerosing cholangitis, Autoimmune hepatitis, Addison's disease, Hashimoto's thyroiditis, Fibromyalgia, Menier's syndrome; transplantation rejection (e.g, prevention of allograft rejection), perniciousanemia, rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, Sjogren's syndrome, lupus erythematosus, multiple sclerosis, myasthenia gravis, Reiter's syndrome, Grave's disease, and other autoimmune disease.

105. A method for treating an anti-checkpoint agent-resistant cancer in a subject in need thereof, the method comprising administering to the subject the pharmaceutical composition of claim 94 or claim 95.

106. The method of claim 105, wherein the anti-checkpoint agent is an antibody, optionally selected from an anti-PD-1, anti-PD-L1, anti-PD-L2, and anti-CTLA antibody.

107. The method of claim 106, wherein the antibody is selected from nivolumab (OPDIVO), pembrolizumab (KEYTRUDA), pidilizumab (CT-011, CURE TECH), MK-3475 (MERCK), BMS 936559, MPDL328OA (ROCHE), Cemiplimab (LIBTAYO), Atezolizumab (TECENTRIQ), Avelumab (BAVENCIO), and Durvalumab (imfinzi).

108. A method of determining a cancer treatment for a patient, the method comprising:(a) obtaining a biological sample from a subject;(b) evaluating the biological sample for the expression of Trim / ; and(c) selecting the cancer therapy comprising the pharmaceutical composition of claim 94 or claim 95 if the Trim / is upregulated compared to a compared to a healthy tissue, a prior biological sample obtained from the subject, or another biological sample from patient that is known to be sensitive to an anti-checkpoint agent; and(d) optionally selecting a second cancer therapy comprising an anti-checkpoint agent, wherein the anticheckpoint agent is selected from an anti-PD-1, anti-PD-L1, anti-PD-L2, and / or anti-CTLA agent, optionally wherein the anti-checkpoint agent is selected from an anti-PD-1, anti-PD-L1, anti-PD-L2, and / or anti-CTLA antibody.

109. A method for selecting a patient for a cancer treatment, the method comprising:(a) obtaining a biological sample from a subject;(b) evaluating the biological sample for the expression of Trim / ; and(c) selecting the cancer therapy comprising the pharmaceutical composition of claim 94 or claim 95 if the Trim / is upregulated compared to a compared to a healthy tissue, a prior biological sample obtained from the subject, or another biological sample from patient that is known to be sensitive to an anti-checkpoint agent; and(d) optionally selecting a second cancer therapy comprising an anti-checkpoint agent, wherein the anticheckpoint agent is selected from an anti-PD-1, anti-PD-L1, anti-PD-L2. and / or anti-CTLA agent, optionally wherein the anti-checkpoint agent is selected from an anti-PD-1, anti-PD-L1, anti-PD-L2, and / or anti-CTLA antibody.

110. A method of treating cancer, the method comprising:(a) obtaining a biological sample from a subject;(b) evaluating the biological sample for the expression of Trim / ;(c) administering the pharmaceutical composition of claim 94 or claim 95.

111. The method of any one of claims 108 to 110, wherein the biological sample is afresh tissue sample, frozen tumor tissue specimen, cultured cells, circulating tumor cells, or a formalin-fixed paraffin-embedded tumor tissue specimen.

112. The method of any one of claims 108 to 111, wherein the biological sample is a biopsy sample, optionally wherein the biopsy sample is selected from endoscopic biopsy, bone marrow biopsy, endoscopic biopsy (e.g., cystoscopy, bronchoscopy and colonoscopy), needle biopsy (e.g., fine-needle aspiration, core needle biopsy, vacuum-assisted biopsy, X-ray-assisted biopsy, computerized tomography (CT)-assisted biopsy, magnetic resonance imaging (MRI)-assisted biopsy and ultrasound-assisted biopsy), skin biopsy (e.g., shave biopsy, punch biopsy, and incisional biopsy) and surgical biopsy.

113. The method of any one of claims 108 to 111, wherein the biological sample comprises a body fluid selected from blood, plasma, serum, lacrimal fluid, tears, bone marrow, blood, blood cells, ascites, tissue or fine needle biopsy sample, cell-containing body fluid, free floating nucleic acids, sputum, saliva, urine, cerebrospinal fluid, peritoneal fluid, pleural fluid, feces, lymph, gynecological fluid, skin swab, vaginal swab, oral swab, nasal swab, washing or lavage such as a ductal lavage or broncheoalveolar lavage, aspirate, scraping, bone marrow specimen, tissue biopsy specimen, surgical specimen, feces, other body fluids, secretions, and / or excretions, and / or cells therefrom.

114. The method of any one of claims 108 to 113, wherein the biological sample comprises at least one tumor cell.

115. The method of any one of claims 108 to 114, wherein the evaluating is performed by DNA sequencing, RNA sequencing, immunohistochemical staining, western blotting, in cell western, immunofluorescent staining, ELISA, and fluorescent activating cell sorting (FACS) or a combination thereof.

116. The method of any one of claims 108 to 115, wherein the evaluating is performed by contacting the sample with an agent that specifically binds to Trim / .

117. The method of claim 116, wherein the agent that specifically binds to one or proteins comprises an antibody, antibody-like molecule or binding a fragment thereof.

118. The method of any one of claims 108 to 115, wherein the evaluating is performed by contacting the sample with an agent that specifically binds to one or more of nucleic acids of Trim7.

119. The method of claim 118, wherein the agent that specifically binds to one or more of the nucleic acids is a nucleic acid primer or probe.

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