Compounds useful in the modulation of klhdc1 and klhdc2 activity

Abstract

This disclosure relates to compounds useful for ex vivo, in vitro, or in vivo modulation of KLHDC1 and KLHDC2 activity. This disclosure also provides pharmaceutically acceptable compositions comprising said compounds, and methods of using the compositions in the treatment of various diseases, conditions, and / or disorders.

Description

[0001] COMPOUNDS USEFUL IN THE MODULATION OF KLHDC1 AND KLHDC2 ACTIVITY CROSS REFERENCE This application claims the benefit of United States Provisional Patent Application No. 63 / 602,189, filed November 22, 2023, the contents of which are incorporated herein by reference in their entirety for all purposes. FIELD This disclosure provides novel compounds for modulation of KLHDC2, and methods for treating diseases affected by subsequent KLHDC2 activity. BACKGROUND Kelch domain containing protein 2 (KLHDC2) was first identified in 2001 as a uniquely novel and ubiquitously expressed protein ligase related to cellular transcriptional cofactors HCF- 1 and HCF-2. Zhou et al. J. Biol. Chem. 2001, 276, 28933. KLHDC2 inhibits LZIP-mediated transcription. Zhou et al. LZIP is a cellular transcription factor that has been implicated in cell proliferation. Zhou et al. KLHDC2 inhibits LZIP via modulation of or interference with the DNA binding activity or capability of LZIP leading to less transcription. Zhou et al. Since LZIP has tumor suppressive activity, expression of KLHDC2 might influence cell proliferation via the inhibition of LZIP. Chin et al. Mol. Cell Biochem.2007, 296, 109. Kelch domain containing protein 1 (KLHDC1) was first identified in 2007 and is a close homolog to KLHDC2 sharing 47% identity and 65% similarity at the amino acid sequence level Chin et al. KLHDC1 degrades truncated oxidoreductive-inactive SELENOS, which is linked to reactive oxygen species production and ER stress induced cell death. Okumura et al. iScience, 2020, 23, 100970. Both KLHDC1 and KLHDC2 have broad expression in all tissues, with elevated expression in some cancers. Notably, KLHDC2 is localized in the nucleus and KLHDC1 is localized in the cytosol. Consequently, if one were interested in inhibiting primarily a nuclear process such as transcription, then inhibiting KLHDC2 would be desired versus inhibiting a primarily cytosolic process were inhibiting KLHDC1 would be desired. For example, it has been shown that inhibiting KLHDC2 can inhibit LZIP-mediated transcription. Described herein are novel small molecules that are recognized by and are useful in modulating KLHDC1, KLHDC2, or both activities. SUMMARY Provided herein are compounds capable of modulating KLHDC1 and KLHDC2 activity. The compounds are useful, for example, in the treatment or prevention of inflammatory, autoimmune, and proliferative diseases and disorders in a subject in need thereof. In one aspect, provided herein is a compound having the following formu or a pharmaceutically acceptable salt thereof, wherein is selected from the group consisting of an aryl, heteroaryl, bicyclic aryl, and bicyclic hete l wherein aryl, heteroaryl, bicyclic aryl, and bicyclic heteroaryl are unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, halo, or heteroaryl; R1is , ; or each R1is further l, heterocycloalkyl, haloalkyl, rogen or alkyl; R6is hydrogen or an amino acid side chain; R7is –OR7a, –NR7aR7b, or , wherein R7aand R7bare independently hydrogen or alkyl; aa is one teroalkyl; R9is aryl, benzo[d][1,3]dioxole, heteroalkyl, or heteroaryl compri rogen, oxygen, or sulfur wherein the aryl and heteroaryl are unsubstituted or substituted with alkyl, –OH, hydroxyalkyl, alkoxy, cyano, pyridazine, and pyrazole; R10is hydrogen, alkyl, or hydroxyalkyl; R11is heteroaryl wherein heteroaryl is unsubstituted or substituted with alkyl, haloalkyl, alkoxy, –OH, –C(O)NR11aR11b, or , wherein R11aand R11bare independently hydrogen or alkyl; X6is oxygen or NR5; t1is one to five; t2is zero or one; R3is hydrogen, , aryl, or heteroaryl, wherein aryl or heteroaryl are unsubstituted or substituted with alkyl, heteroalkyl, heterocycloalkyl, and / or halo; X5is nitrogen or oxygen; R3ais hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, five- to fifteen-membered spiro bicyclic heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl; –C(O)-(three- to -eight- membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl); three- to -eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl; -alkylene-(three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl); -alkylene-N(R3aa)C(O)alkyl wherein R3aais hydrogen or alkyl; or absent when X5is oxygen; R3bis hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl; and R3crepresents one, two, or three hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, cyano, alkoxy, or halo. In one aspect, provided herein is a compound having the following formula

[0002] or a pharmaceutically acceptable salt thereof, wherein is ; ; ; ; ; or ; wherein X1is CH, C-OH, C-alkyl, C-alkoxy, C-haloalkoxy, or nitrogen; X1ais CH, C-OH, C-alkyl, C-alkoxy, C-haloalkoxy, or nitrogen; X2is CH, C-OH, C-alkyl, C-alkoxy, C-haloalkoxy, or nitrogen; X3is carbon or nitrogen; X4is nitrogen or oxygen; Y is CH or nitrogen; is a single bond or a double bond; R1is , , , , , , , , , or ; or each R1is further substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, halo, or heteroaryl, wherein each R1ais independently -CH2- or -C(O)- and R1bis independently -CH2- or -NH-; R5is independently hydrogen alkyl, or cycloalkyl; R6is hydrogen or an amino acid side chain; R7is –OR7a, –NR7aR7b, or , wherein R7aand R7bare independently hydrogen or alkyl; aa is one to five;R8 is heteroalkyl; R9 is , , or ,wherein is aryl or heteroaryl, wherein aryl or heteroaryl is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, halo, or heteroaryl; each R9ais independently hydrogen or alkyl; R9bis -C(O)OR9cor ; each R9cis hydrogen or C1-5alkyl; and bb is one or two; cc is zero, one, or two; aryl, benzo[d][1,3]dioxole, heteroalkyl, or heteroaryl comprising at least one nitrogen, oxygen, or sulfur wherein the aryl and heteroaryl are unsubstituted or substituted with alkyl, –OH, hydroxyalkyl, alkoxy, cyano, pyridazine, and pyrazole; R10is hydrogen, alkyl, or hydroxyalkyl; R11is heteroaryl wherein heteroaryl is unsubstituted or substituted with alkyl, haloalkyl, alkoxy, –OH, –C(O)NR11aR11b, or , wherein R11aand R11bare independently hydrogen or alkyl; X6is oxygen or NR5; t1is one to five; t2is zero or one; R2is, independently, one to three of hydrogen, –OH, –SH, –S-alkyl, –NR7aR7b, alkyl, alkoxy, or haloalkoxy; R3, when present, is hydrogen, , , aryl, or heteroaryl, wherein aryl or heteroaryl are unsubstituted or substituted with alkyl, heteroalkyl, heterocycloalkyl, and / or halo; X5is nitrogen or oxygen; R3ais hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, five- to fifteen-membered spiro bicyclic heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl; –C(O)-(three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, or –C(O)-alkylene-C(O)R3aaawherein R3aaais –OR7a, –NR7aR7bor alkyl); three- to -eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl; -alkylene-(three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl); -alkylene-N(R3aa)C(O)alkyl wherein R3aais hydrogen or alkyl; –C(O)-alkylene-C(O)R3aaawherein R3aaais –OR7a, –NR7aR7bor alkyl; or absent when X5is oxygen; R3bis hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl; R3crepresents one, two, or three hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, cyano, alkoxy, or halo; R4, when present, is hydrogen, alkyl, haloalkyl, arylalkyl, aryl, heteroaryl, or heterocycloalkyl, wherein aryl, heteroaryl, or heterocycloalkyl are unsubstituted or substituted with alkyl, alkenyl, alkynyl, heteroalkyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, –C(O)-alkylene-C(O)R3aaawherein R3aaais –OR7a, –NR7aR7bor alkyl; or –C(O)NR4aR4bwherein R4aand R4bare independently hydrogen or alkyl; a five- to fifteen- membered spiro bicyclic heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, or –C(O)-alkylene-C(O)R3aaawherein R3aaais –OR7a, –NR7aR7bor alkyl; –NR4aR4bwherein R4aand R4bare independently hydrogen, alkyl, aryl, heteroaryl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, or arylalkyl; three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl, –C(O)-heteroalkylene-NR4aR4b, alkyl, –C(O)-alkylene-COOR5, –C(O)-alkylene-C(O)NR4aR4b, –C(O)-alkylene-C(O)N(R4a)-heteroalkylene-halo, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl, wherein R4aand R4bare independently hydrogen, alkyl, or acyl; -alkylene-NR4aR4bwherein R4aand R4bare independently hydrogen, alkyl, or acyl; or –N(R5)C(O)-alkylene-NR4aR4bwherein R4aand R4bare independently hydrogen, alkyl, or acyl. In one aspect, provided herein is a compound having the following formula or a pharmaceutically acceptable salt thereof, wherein is ; ; ; ; or ; wherein X1is CH, C-OH, C-alkyl, C-alkoxy, C-haloalkoxy, or nitrogen; X1ais CH, C-OH, C-alkyl, C-alkoxy, C-haloalkoxy, or nitrogen; X2is CH, C-OH, C-alkyl, C-alkoxy, C-haloalkoxy, or nitrogen; X3is carbon or nitrogen; X4is nitrogen or oxygen; Y is CH or nitrogen; is a single bond or a double bond; R1is , , , , , , , , , or ; or each R1is further substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, halo, or heteroaryl, wherein each R1ais independently -CH2- or -C(O)- and R1bis independently -CH2- or -NH-; R5is independently hydrogen or alkyl; R6is hydrogen or an amino acid side chain; R7is –OR7a, –NR7aR7b, or , wherein R7aand R7bare independently hydrogen or alkyl; aa is one to five; R8is heteroalkyl; R9is aryl, benzo[d][1,3]dioxole, heteroalkyl, or heteroaryl comprising at least one nitrogen, oxygen, or sulfur wherein the aryl and heteroaryl are unsubstituted or substituted with alkyl, –OH, hydroxyalkyl, alkoxy, cyano, pyridazine, and pyrazole; R10is hydrogen, alkyl, or hydroxyalkyl; R11is heteroaryl wherein heteroaryl is unsubstituted or substituted with alkyl, haloalkyl, alkoxy, –OH, –C(O)NR11aR11b, or , wherein R11aand R11bare independently hydrogen or alkyl; X6is oxygen or NR5; t1is one to five; t2is zero or one; R2is, independently, one to three of hydrogen, –OH, alkyl, alkoxy, or haloalkoxy; R3, when present, is hydrogen, , aryl, or heteroaryl, wherein aryl or heteroaryl are unsubstituted or substituted with alkyl, heteroalkyl, heterocycloalkyl, and / or halo; X5is nitrogen or oxygen; R3ais hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, five- to fifteen-membered spiro bicyclic heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl; –C(O)-(three- to -eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl); three- to -eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl; -alkylene-(three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl); -alkylene-N(R3aa)C(O)alkyl wherein R3aais hydrogen or alkyl; or absent when X5is oxygen; R3bis hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl; R3crepresents one, two, or three hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, cyano, alkoxy, or halo; R4, when present, is hydrogen, alkyl, haloalkyl, arylalkyl, aryl, heteroaryl, or heterocycloalkyl, wherein aryl, heteroaryl, or heterocycloalkyl are unsubstituted or substituted with alkyl, alkenyl, alkynyl, heteroalkyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, or –C(O)NR4aR4bwherein R4aand R4bare independently hydrogen or alkyl; a five- to fifteen-membered spiro bicyclic heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl; –NR4aR4bwherein R4aand R4bare independently hydrogen, alkyl, aryl, heteroaryl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, or arylalkyl; three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl, –C(O)-heteroalkylene-NR4aR4b, alkyl, –C(O)-alkylene-COOR5, –C(O)-alkylene-C(O)NR4aR4b, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl, wherein R4aand R4bare independently hydrogen, alkyl, or acyl; -alkylene-NR4aR4bwherein R4aand R4bare independently hydrogen, alkyl, or acyl; or –N(R5)C(O)-alkylene-NR4aR4bwherein R4aand R4bare independently hydrogen, alkyl, or acyl. In one aspect, provided herein is a compound having the following formula or a pharmaceutically acceptable salt thereof, wherein is ; ; or ; wherein X1is CH or nitrogen; X2is CH or nitrogen; X3

[0003] is carbon or nitrogen; X4is nitrogen or oxygen; Y is CH or nitrogen; R1is , , , , , , , , , or , wherein R5is independently hydrogen or alkyl; R6is hydrogen or an amino acid side chain; R7is –OR7a, –NR7aR7b, or , wherein R7aand R7bare independently hydrogen or alkyl; aa is one to five; R8is heteroalkyl; R9is aryl, benzo[d][1,3]dioxole, heteroalkyl, or heteroaryl comprising at least one nitrogen, oxygen, or sulfur wherein the aryl and heteroaryl are unsubstituted or substituted with alkyl, –OH, hydroxyalkyl, alkoxy, cyano, pyridazine, and pyrazole; R10is hydrogen, alkyl, or hydroxyalkyl; R11is heteroaryl wherein heteroaryl is unsubstituted or substituted with alkyl, haloalkyl, alkoxy, –OH, –C(O)NR11aR11b, or , wherein R11aand R11bare independently hydrogen or alkyl; X6is oxygen or NR5; t1is one to five; t2is zero or one; R2is, independently, one to three of hydrogen, –OH, alkyl, alkoxy, or haloalkoxy; R3, when present, is hydrogen, , aryl, or heteroaryl, wherein aryl or heteroaryl are unsubstituted or substituted with alkyl, heteroalkyl, heterocycloalkyl, and / or halo; X5is nitrogen or oxygen; R3ais hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, five- to fifteen-membered spiro bicyclic heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl, –C(O)-(three- to -eight- membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl), three- to -eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl, -alkylene-(three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl), or absent when X5is oxygen; R3bis hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl; R3cis hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, cyano, or halo; R4, when present, is hydrogen, alkyl, haloalkyl, arylalkyl, aryl, heteroaryl, or heterocycloalkyl, wherein aryl, heteroaryl, or heterocycloalkyl are unsubstituted or substituted with alkyl, alkenyl, alkynyl, heteroalkyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl; a five- to fifteen-membered spiro bicyclic heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl; –NR4aR4bwherein R4aand R4bare independently hydrogen, alkyl, aryl, heteroaryl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, or arylalkyl; three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl, –C(O)-heteroalkylene-NR4aR4b, alkyl, –C(O)-alkylene-COOR5, –C(O)-alkylene-C(O)NR4aR4b, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl, wherein R4aand R4bare independently hydrogen, alkyl, or acyl; -alkylene-NR4aR4bwherein R4aand R4bare independently hydrogen, alkyl, or acyl; or –N(R5)C(O)-alkylene-NR4aR4bwherein R4aand R4bare independently hydrogen, alkyl, or acyl.

[0004] In one aspect, provided herein is a compound having the following formula or a pharmaceutically acceptable salt thereof, wherein each is independently arylene or heteroarylene wherein arylene or heteroarylene are unsubstituted or substituted with one or more alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, halo, heteroaryl, or –C(O)NR1R2, wherein R1and R2are independently hydrogen or alkyl; is cycloalkylene or heterocycloalkylene wherein cycloalkylene or heterocycloalkylene are unsubstituted or substituted with one or more alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, halo, heteroaryl, or –C(O)NR1R2, wherein R1and R2are independently hydrogen or alkyl; each X1is -N(R3)-, oxygen, or sulfur wherein R3is hydrogen or alkyl; X2is N(R4), oxygen, or sulfur, wherein R4is hydrogen or alkyl; and each n is an integer from one to five. In one aspect, provided herein is a compound having the following formula or a pharmaceutically acceptable salt thereof, wherein is cycloalkylene or heterocycloalkylene wherein cycloalkylene or heterocycloalkylene are unsubstituted or substituted with one or more alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, halo, heteroaryl, or –C(O)NRaRb, wherein Raand Rbare independently hydrogen or alkyl; is arylene or heteroarylene wherein arylene or heteroarylene are unsubstituted or substituted with one or more alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, halo, heteroaryl, or –C(O)NRaRb, wherein Raand Rbare independently hydrogen or alkyl; each R1is independently hydrogen or alkyl; R2is hydrogen or alkyl; and each n is independently an integer from one to eight. In one aspect, provided is a compound having the following formula or a pharmaceutically acceptable salt thereof, wherein and are independently arylene or heteroarylene wherein arylene or heteroarylene are unsubstituted or substituted with one or more alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, halo, heteroaryl, or –C(O)NRaRb, wherein Raand Rbare independently hydrogen or alkyl; each R1is independently hydrogen or alkyl; R2is hydrogen or alkyl; and each n is independently an integer from one to eight. In another aspect, provided herein are pharmaceutical compositions. The pharmaceutical compositions include a compound having the following formula described herein, along with one or more pharmaceutically acceptable carriers, diluents, and / or excipients. In another aspect, provided herein are methods of treating a disease or disorder in a subject in need thereof comprising the step of administering to the subject a therapeutically effective amount of the compound having the following formula described herein, or pharmaceutical compositions thereof to the subject. In certain embodiments, provided herein are the compounds and compositions having the following formula described herein for use in therapy. In certain embodiments, provided herein are the compounds and compositions having the following formula described herein for use in the treatment or prevention of inflammatory, autoimmune, or proliferative diseases and disorders. In certain embodiments, provided herein are uses of the compounds and compositions having the following formula described herein for the manufacture of medicaments. In certain embodiments, provided herein are uses of the compounds and compositions having the following formula described herein for the manufacture of medicaments for the treatment or prevention of inflammatory, autoimmune, or proliferative diseases and disorders. In certain embodiments, the disease or disorder is an autoimmune disease or disorder. In certain embodiments, the disease or disorder is a proliferative disease or disorder, for instance, a T-cell lymphoma. In certain embodiments, the disease or disorder is cancer. In certain embodiments, the compounds or compositions having the following formula described herein are for use in the treatment of cancer. DETAILED DESCRIPTION Definitions For purposes herein, the chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75th Ed. Addition al principles of organic chemistry are described in “Organic Chemistry,” Thomas niversity Science Books, Sausalito: 1999, and “March’s Advanced Organic Chemist , Ed.: Smith, M.B. and March, J., John Wiley & Sons, New York: 2001, the entire contents of which are hereby incorporated herein by reference. As described herein, “protecting group” refers to a moiety or functionality that is introduced into a molecule by chemical modification of a functional group in order to obtain chemoselectivity in a subsequent chemical reaction. Standard protecting groups are provided in Wuts and Greene: “Greene’s Protective Groups in Organic Synthesis,” 4th Ed, Wuts, P.G.M. and Greene, T.W., Wiley-Interscience, New York: 2006. As described herein, compounds herein optionally may be substituted with one or more substituents, such as those illustrated generally herein, or as exemplified by particular classes, subclasses, and / or species of this description. As used herein, the term “hydroxyl” or “hydroxy” refers to an –OH moiety. As used herein, the term “aliphatic” encompasses the terms alkyl, alkenyl, and alkynyl, each of which are optionally substituted as set forth below. As used herein, an “alkyl” or divalent “alkylene” group refers to a saturated aliphatic hydrocarbon group containing one to twelve (e.g., one to eight, one to six, or one to four) carbon atoms. An alkyl or alkylene group can be straight or branched. Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert- butyl, n-pentyl, n-heptyl, or 2-ethylhexyl. Examples of alkylene groups include, but are not limited to, -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, -CH2CH2CH2CH2CH2-, or -CH2CH2CH2CH2CH2CH2- An alkyl or alkylene group can be substituted (i.e., optionally substituted) with one or more substituents such as halo, phospho, cycloaliphatic (e.g., cycloalkyl or cycloalkenyl), heterocycloaliphatic (e.g., heterocycloalkyl or heterocycloalkenyl), aryl, heteroaryl, alkoxy, aroyl, heteroaroyl, acyl (e.g., (aliphatic)carbonyl, (cycloaliphatic)carbonyl, or (heterocycloaliphatic)carbonyl), nitro, cyano (i.e., -CN), amido (e.g., (cycloalkylalkyl)carbonylamino, arylcarbonylamino, aralkylcarbonylamino, (heterocycloalkyl)carbonylamino, (heterocycloalkylalkyl)carbonylamino, heteroarylcarbonylamino, heteroaralkylcarbonylamino, alkylaminocarbonyl, cycloalkylaminocarbonyl, heterocycloalkylaminocarbonyl, arylaminocarbonyl, or heteroarylaminocarbonyl), amino (e.g., aliphaticamino, cycloaliphaticamino, or heterocycloaliphaticamino), sulfonyl (e.g., aliphatic-SO2-, cycloaliphatic-SO2-, or aryl-SO2-), sulfinyl, sulfanyl, sulfoxy, urea, thiourea, sulfamoyl, sulfamide, oxo, carboxy, carbamoyl, cycloaliphaticoxy, heterocycloaliphaticoxy, aryloxy, heteroaryloxy, aralkyloxy, heteroarylalkoxy, alkoxycarbonyl, alkylcarbonyloxy, or hydroxy. Without limitation, some examples of substituted alkyls include carboxyalkyl (such as HOOC-alkyl, alkoxycarbonylalkyl, and alkylcarbonyloxyalkyl), cyanoalkyl, hydroxyalkyl, alkoxyalkyl, acylalkyl, aralkyl, (alkoxyaryl)alkyl, (sulfonylamino)alkyl (such as (alkyl-SO2-amino)alkyl), aminoalkyl, amidoalkyl, (cycloaliphatic)alkyl, or haloalkyl. As used herein, an “alkenyl” group refers to an aliphatic carbon group that contains two to eight (e.g., two to four or two to six) carbon atoms and at least one double bond. Like an alkyl group, an alkenyl group can be straight or branched. Examples of an alkenyl group include, but are not limited to, allyl, 1- or 2-isopropenyl, 2-butenyl, and 2-hexenyl. An alkenyl group can be optionally substituted with one or more substituents such as halo, phospho, cycloaliphatic (e.g., cycloalkyl or cycloalkenyl), heterocycloaliphatic (e.g., heterocycloalkyl or heterocycloalkenyl), aryl, heteroaryl, alkoxy, aroyl, heteroaroyl, acyl (e.g., (aliphatic)carbonyl, (cycloaliphatic)carbonyl, or (heterocycloaliphatic)carbonyl), nitro, cyano, amido (e.g., (cycloalkylalkyl)carbonylamino, arylcarbonylamino, aralkylcarbonylamino, (heterocycloalkyl)carbonylamino, (heterocycloalkylalkyl)carbonylamino, heteroarylcarbonylamino, heteroaralkylcarbonylamino, alkylaminocarbonyl, cycloalkylaminocarbonyl, heterocycloalkylaminocarbonyl, arylaminocarbonyl, or heteroarylaminocarbonyl), amino (e.g., aliphaticamino, cycloaliphaticamino, heterocycloaliphaticamino, or aliphaticsulfonylamino), sulfonyl (e.g., alkyl-SO2-, cycloaliphatic- SO2-, or aryl-SO2-), sulfinyl, sulfanyl, sulfoxy, urea, thiourea, sulfamoyl, sulfamide, oxo, carboxy, carbamoyl, cycloaliphaticoxy, heterocycloaliphaticoxy, aryloxy, heteroaryloxy, aralkyloxy, heteroaralkoxy, alkoxycarbonyl, alkylcarbonyloxy, or hydroxy. Without limitation, some examples of substituted alkenyls include cyanoalkenyl, alkoxyalkenyl, acylalkenyl, hydroxyalkenyl, aralkenyl, (alkoxyaryl)alkenyl, (sulfonylamino)alkenyl (such as (alkyl-SO2-amino)alkenyl), aminoalkenyl, amidoalkenyl, (cycloaliphatic)alkenyl, or haloalkenyl. As used herein, an “alkynyl” group refers to an aliphatic carbon group that contains two to eight (e.g., two to four or two to six) carbon atoms and has at least one triple bond. An alkynyl group can be straight or branched. Examples of an alkynyl group include, but are not limited to, propargyl and butynyl. An alkynyl group can be optionally substituted with one or more substituents such as aroyl, heteroaroyl, alkoxy, cycloalkyloxy, heterocycloalkyloxy, aryloxy, heteroaryloxy, aralkyloxy, nitro, carboxy, cyano, halo, hydroxy, sulfo, mercapto, sulfanyl (e.g., aliphaticsulfanyl or cycloaliphaticsulfanyl), sulfinyl (e.g., aliphaticsulfinyl or cycloaliphaticsulfinyl), sulfonyl (e.g., aliphatic-SO2-, aliphaticamino-SO2-, or cycloaliphatic-SO2-), amido (e.g., aminocarbonyl, alkylaminocarbonyl, alkylcarbonylamino, cycloalkylaminocarbonyl, heterocycloalkylaminocarbonyl, cycloalkylcarbonylamino, arylaminocarbonyl, arylcarbonylamino, aralkylcarbonylamino, (heterocycloalkyl)carbonylamino, (cycloalkylalkyl)carbonylamino, heteroaralkylcarbonylamino, heteroarylcarbonylamino, or heteroarylaminocarbonyl), urea, thiourea, sulfamoyl, sulfamide, alkoxycarbonyl, alkylcarbonyloxy, cycloaliphatic, heterocycloaliphatic, aryl, heteroaryl, acyl (e.g., (cycloaliphatic)carbonyl or (heterocycloaliphatic)carbonyl), amino (e.g., aliphaticamino), sulfoxy, oxo, carboxy, carbamoyl, (cycloaliphatic)oxy, (heterocycloaliphatic)oxy, or (heteroaryl)alkoxy. As used herein, “heteroalkyl” refers to an alkyl in which one or more carbon atoms are replaced by heteroatoms. As used herein, “heteroalkenyl” refers to an alkenyl in which one or more carbon atoms are replaced by heteroatoms. As used herein, “heteroalkynyl” refers to an alkynyl in which one or more carbon atoms are replaced by heteroatoms. Suitable heteroatoms include, but are not limited to, halo, nitrogen, oxygen, and sulfur atoms. Heteroalkyl, heteroalkenyl, and heteroalkynyl are optionally substituted. Examples of heteroalkyl moieties include, but are not limited to, aminoalkyl, sulfonylalkyl, and sulfinylalkyl. Examples of heteroalkyl moieties also include, but are not limited to, methylamino, methylsulfonyl, and methylsulfinyl. As used herein, an “amido” group encompasses both “aminocarbonyl” and “carbonylamino.” These terms when used alone or in connection with another group refer to an amido group such as -N(RX)-C(O)-RYor -C(O)-N(RX)2 when used terminally, and -C(O)-N(RX)- or -N(RX)-C(O)- when used internally, wherein RXand RYcan be aliphatic, cycloaliphatic, aryl, araliphatic, heterocycloaliphatic, heteroaryl, or heteroaraliphatic. Examples of amido groups include alkylamido (such as alkylcarbonylamino or alkylaminocarbonyl), (heterocycloaliphatic)amido, (heteroaralkyl)amido, (heteroaryl)amido, (heterocycloalkyl)alkylamido, arylamido, aralkylamido, (cycloalkyl)alkylamido, or cycloalkylamido. As used herein, an “amino” group refers to -NRXRYwherein each of RXand RYis independently hydrogen (H or –H), aliphatic, cycloaliphatic, (cycloaliphatic)aliphatic, aryl, araliphatic, heterocycloaliphatic, (heterocycloaliphatic)aliphatic, heteroaryl, carboxy, sulfanyl, sulfinyl, sulfonyl, (aliphatic)carbonyl, (cycloaliphatic)carbonyl, ((cycloaliphatic)aliphatic)carbonyl, arylcarbonyl, (araliphatic)carbonyl, (heterocycloaliphatic)carbonyl, ((heterocycloaliphatic)aliphatic)carbonyl, (heteroaryl)carbonyl, or (heteroaraliphatic)carbonyl, each of which being defined elsewhere herein and being optionally substituted. Examples of amino groups include alkylamino, dialkylamino, or arylamino. When the term “amino” is not the terminal group (e.g., alkylcarbonylamino), it is represented by -NRX-, where RXhas the same meaning as defined above. As used herein, an “aryl” group used alone or as part of a larger moiety as in “aralkyl,” “aralkoxy,” or “aryloxyalkyl” refers to monocyclic (e.g., phenyl); bicyclic (e.g., indenyl, naphthalenyl, tetrahydronaphthyl, or tetrahydroindenyl); and tricyclic (e.g., fluorenyl tetrahydrofluorenyl, tetrahydroanthracenyl, or anthracenyl) ring systems in which the monocyclic ring system is aromatic or at least one of the rings in a bicyclic or tricyclic ring system is aromatic. The bicyclic and tricyclic groups include benzofused (e.g., 2- or 3-membered, or bi- or tricyclic carbocyclic) rings. For example, a benzofused group includes phenyl fused with two or more C4-8 carbocyclic moieties. An aryl is optionally substituted with one or more substituents including aliphatic (e.g., alkyl, alkenyl, or alkynyl); cycloaliphatic; (cycloaliphatic)aliphatic; heterocycloaliphatic; (heterocycloaliphatic)aliphatic; aryl; heteroaryl; alkoxy; (cycloaliphatic)oxy; (heterocycloaliphatic)oxy; aryloxy; heteroaryloxy; (araliphatic)oxy; (heteroaraliphatic)oxy; aroyl; heteroaroyl; amino; oxo (i.e., on a non-aromatic carbon within a carbocyclic ring of a benzofused bicyclic or tricyclic aryl); nitro; carboxy; amido; acyl (e.g., (aliphatic)carbonyl; (cycloaliphatic)carbonyl; ((cycloaliphatic)aliphatic)carbonyl; (araliphatic)carbonyl; (heterocycloaliphatic)carbonyl; ((heterocycloaliphatic)aliphatic)carbonyl; or (heteroaraliphatic)carbonyl); sulfonyl (e.g., aliphatic-SO2- or amino-SO2-); sulfinyl (e.g., aliphatic-S(O)- or cycloaliphatic-S(O)-); sulfanyl (e.g., aliphatic-S-); cyano; halo; hydroxy; mercapto; sulfoxy; urea; thiourea; sulfamoyl; sulfamide; or carbamoyl. Alternatively, an aryl can be unsubstituted. Non-limiting examples of substituted aryls include haloaryl (e.g., mono-, di- (such as p,m-dihaloaryl), and (tri-halo)aryl); (carboxy)aryl (e.g., (alkoxycarbonyl)aryl, ((aralkyl)carbonyloxy)aryl, and (alkoxycarbonyl)aryl); (amido)aryl (e.g., (aminocarbonyl)aryl, (((alkylamino)alkyl)aminocarbonyl)aryl, (alkylcarbonyl)aminoaryl, (arylaminocarbonyl)aryl, and (((heteroaryl)amino)carbonyl)aryl); aminoaryl (e.g., ((alkylsulfonyl)amino)aryl or ((dialkyl)amino)aryl); (cyanoalkyl)aryl; (alkoxy)aryl; (sulfamoyl)aryl (e.g., (aminosulfonyl)aryl); (alkylsulfonyl)aryl; (cyano)aryl; (hydroxyalkyl)aryl; ((alkoxy)alkyl)aryl; (hydroxy)aryl, ((carboxy)alkyl)aryl; (((dialkyl)amino)alkyl)aryl; (nitroalkyl)aryl; (((alkylsulfonyl)amino)alkyl)aryl; ((heterocycloaliphatic)carbonyl)aryl; ((alkylsulfonyl)alkyl)aryl; (cyanoalkyl)aryl; (hydroxyalkyl)aryl; (alkylcarbonyl)aryl; alkylaryl; (trihaloalkyl)aryl; p-amino-m-alkoxycarbonylaryl; p-amino-m-cyanoaryl; p-halo-m-aminoaryl; or (m-(heterocycloaliphatic)-o-(alkyl))aryl. As used herein, an “araliphatic” such as an “aralkyl” group refers to an aliphatic group (e.g., a C1-4alkyl group) that is substituted with an aryl group. “Aliphatic,” “alkyl,” and “aryl” are defined elsewhere herein. An example of an araliphatic such as an aralkyl group is benzyl. As used herein, an “aralkyl” group refers to an alkyl group (e.g., a C1-4alkyl group) that is substituted with an aryl group. Both “alkyl” and “aryl” have been defined above. An example of an aralkyl group is benzyl. An aralkyl is optionally substituted with one or more substituents such as aliphatic (e.g., alkyl, alkenyl, or alkynyl, including carboxyalkyl, hydroxyalkyl, or haloalkyl such as trifluoromethyl), cycloaliphatic (e.g., cycloalkyl or cycloalkenyl), (cycloalkyl)alkyl, heterocycloalkyl, (heterocycloalkyl)alkyl, aryl, heteroaryl, alkoxy, cycloalkyloxy, heterocycloalkyloxy, aryloxy, heteroaryloxy, aralkyloxy, heteroaralkyloxy, aroyl, heteroaroyl, nitro, carboxy, alkoxycarbonyl, alkylcarbonyloxy, amido (e.g., aminocarbonyl, alkylcarbonylamino, cycloalkylcarbonylamino, (cycloalkylalkyl)carbonylamino, arylcarbonylamino, aralkylcarbonylamino, (heterocycloalkyl)carbonylamino, (heterocycloalkylalkyl)carbonylamino, heteroarylcarbonylamino, or heteroaralkylcarbonylamino), cyano, halo, hydroxy, acyl, mercapto, alkylsulfanyl, sulfoxy, urea, thiourea, sulfamoyl, sulfamide, oxo, or carbamoyl. As used herein, a “bicyclic ring system” includes 6- to 12-membered (e.g., 8- to 12- or 9-, 10-, or 11-membered) structures that form two rings, wherein the two rings have at least one atom in common (e.g., two atoms in common). Bicyclic ring systems include bicycloaliphatics (e.g., bicycloalkyl or bicycloalkenyl), bicycloheteroaliphatics, bicyclic aryls, and bicyclic heteroaryls. As used herein, a “cycloaliphatic” group encompasses a “cycloalkyl” group and a “cycloalkenyl” group, each of which are optionally substituted as set forth below. As used herein, a “cycloalkyl” group refers to a saturated carbocyclic mono- or bicyclic (fused, bridged, or spiro) ring of three to ten (e.g., five to ten) carbon atoms. Examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, adamantyl, norbornyl, cubyl, octahydro-indenyl, decahydro-naphthyl, bicyclo[3.2.1]octyl, bicyclo[2.2.2]octyl, bicyclo[3.3.1]nonyl, bicyclo[3.3.2]decyl, bicyclo[2.2.2]octyl, adamantyl, spiro[3.3]heptanyl, or ((aminocarbonyl)cycloalkyl)cycloalkyl. A “cycloalkenyl” group, as used herein, refers to a non-aromatic carbocyclic ring of three to ten (e.g., four to eight) carbon atoms having one or more double bonds. Examples of cycloalkenyl groups include cyclopentenyl, 1,4-cyclohexa-di-enyl, cycloheptenyl, cyclooctenyl, hexahydro-indenyl, octahydro-naphthyl, cyclohexenyl, bicyclo[2.2.2]octenyl, or bicyclo[3.3.1]nonenyl. A “cycloalkyl” or “cycloalkenyl” group can be optionally substituted with one or more substituents such as phospho, aliphatic (e.g., alkyl, alkenyl, or alkynyl), cycloaliphatic, (cycloaliphatic)aliphatic, heterocycloaliphatic, (heterocycloaliphatic)aliphatic, aryl, heteroaryl, alkoxy, (cycloaliphatic)oxy, (heterocycloaliphatic)oxy, aryloxy, heteroaryloxy, (araliphatic)oxy, (heteroaraliphatic)oxy, aroyl, heteroaroyl, amino, amido (e.g., (aliphatic)carbonylamino, (cycloaliphatic)carbonylamino, ((cycloaliphatic)aliphatic)carbonylamino, (aryl)carbonylamino, (araliphatic)carbonylamino, (heterocycloaliphatic)carbonylamino, ((heterocycloaliphatic)aliphatic)carbonylamino, (heteroaryl)carbonylamino, or (heteroaraliphatic)carbonylamino), nitro, carboxy (e.g., HOOC-, alkoxycarbonyl, or alkylcarbonyloxy), acyl (e.g., (cycloaliphatic)carbonyl, ((cycloaliphatic)aliphatic)carbonyl, (araliphatic)carbonyl, (heterocycloaliphatic)carbonyl, ((heterocycloaliphatic)aliphatic)carbonyl, or (heteroaraliphatic)carbonyl, cyano, halo, hydroxy, mercapto, sulfonyl (e.g., alkyl-SO2- and aryl- SO2-), sulfinyl (e.g., alkyl-S(O)-), sulfanyl (e.g., alkyl-S-), sulfoxy, urea, thiourea, sulfamoyl, sulfamide, oxo, or carbamoyl. As used herein, the term “heterocycloaliphatic” encompasses heterocycloalkyl groups and heterocycloalkenyl groups, each of which being optionally substituted as set forth below. As used herein, a “heterocycloalkyl” or divalent “heterocycloalklene” group refers to a 3- to 15-membered mono- or bicylic (e.g., 5- to 10-membered mono- or bicyclic) saturated ring structure (e.g., fused, bridged, or spiro), in which one or more of the ring atoms is a heteroatom (e.g., nitrogen (N), oxygen (O), sulfur (S), or combinations thereof). Non-limiting examples of a heterocycloalkyl (or a divalent heterocycloalkylene) group include piperidyl or piperidinyl, piperazyl or piperazinyl, tetrahydropyranyl, tetrahydrofuryl or tetrahydrofuranyl, 1,4-dioxolanyl, 1,4-dithianyl, 1,3-dioxolanyl, oxazolidyl or oxazolidinyl, isoxazolidyl or isoxazolidinyl, morpholinyl, thiomorpholinyl, octahydrobenzofuryl or octahydrobenzofuranyl, octahydrochromenyl, octahydrothiochromenyl, octahydroindolyl or octahydroindolinyl, octahydropyrindinyl or octahydro-1H-cyclopenta[x]pyridine where x is b or c, decahydroquinolinyl, octahydrobenzo[b]thiopheneyl, 2-oxa-bicyclo[2.2.2]octyl, 1-aza- bicyclo[2.2.2]octyl, 3-aza-bicyclo[3.2.1]octyl, 3,8-diazabicyclo[3.2.1]octyl, decahydro-2,7- naphthyridine, 2,8-diazaspiro[4.5]decane, 2-azaspiro[3.3]heptane, 2-azaspiro[3.5]nonane, 3- azaspiro[5.5]undecane, 2,7-diazaspiro[3.5]nonane, octahydropyrrolo[3,4-c]pyrrole, octahydro- 1H-pyrrolo[3,4-b]pyridine, 2,5-diazabicyclo[2.2.1]heptane, 1-oxa-8-azaspiro[4.5]decane, and 2,6- dioxa-tricyclo[3.3.1.03,7]nonyl. A monocyclic heterocycloalkyl group can be fused with a phenyl moiety to form, for example, tetrahydroisoquinoline, that could be categorized as a heteroaryl as defined elsewhere herein. A “heterocycloalkenyl” group, as used herein, refers to a mono- or bicylic (e.g., 5- to 10-membered mono- or bicyclic) non-aromatic ring structure having one or more double bonds, and wherein one or more of the ring atoms is a heteroatom (e.g., nitrogen (N), oxygen (O), or sulfur (S)). Monocyclic and bicyclic heterocycloalkenyls are numbered according to standard chemical nomenclature. A heterocycloalkyl or heterocycloalkenyl group can be optionally substituted with one or more substituents such as phospho, aliphatic (e.g., alkyl, alkenyl, or alkynyl), cycloaliphatic, (cycloaliphatic)aliphatic, heterocycloaliphatic, (heterocycloaliphatic)aliphatic, aryl, heteroaryl, alkoxy, (cycloaliphatic)oxy, (heterocycloaliphatic)oxy, aryloxy, heteroaryloxy, (araliphatic)oxy, (heteroaraliphatic)oxy, aroyl, heteroaroyl, amino, amido (e.g., (aliphatic)carbonylamino, (cycloaliphatic)carbonylamino, ((cycloaliphatic)aliphatic)carbonylamino, (aryl)carbonylamino, (araliphatic)carbonylamino, (heterocycloaliphatic)carbonylamino, ((heterocycloaliphatic)aliphatic)carbonylamino, (heteroaryl)carbonylamino, or (heteroaraliphatic)carbonylamino, nitro, carboxy (e.g., HOOC-, alkoxycarbonyl, or alkylcarbonyloxy), acyl (e.g., (cycloaliphatic)carbonyl, ((cycloaliphatic)aliphatic)carbonyl, (araliphatic)carbonyl, (heterocycloaliphatic)carbonyl, ((heterocycloaliphatic)aliphatic)carbonyl, or (heteroaraliphatic)carbonyl), nitro, cyano, halo, hydroxy, mercapto, sulfonyl (e.g., alkylsulfonyl or arylsulfonyl), sulfinyl (e.g., alkylsulfinyl), sulfanyl (e.g., alkylsulfanyl), sulfoxy, urea, thiourea, sulfamoyl, sulfamide, oxo, or carbamoyl. A “heteroaryl” group, as used herein, refers to a monocyclic, bicyclic, or tricyclic ring system having four to fifteen ring atoms wherein one or more of the ring atoms is a heteroatom (e.g., N, O, S, or combinations thereof) and in which the monocyclic ring system is aromatic or at least one of the rings in the bicyclic or tricyclic ring systems is aromatic. A heteroaryl group includes a benzofused ring system having two to three rings. For example, a benzofused group includes one or two 4- to 8-membered heterocycloaliphatic moieties (e.g., indolizyl, indolyl, isoindolyl, isoindolinyl-1,3-dione, isoindolinyl-1-one, 3H-indolyl, indolinyl, benzo[b]furyl, benzo[b]thiopheneyl, quinolinyl, or isoquinolinyl). Some examples of heteroaryl are pyridyl, 1H- indazolyl, furyl or furanyl, pyrrolyl, thienyl, thiazolyl, oxazolyl, imidazolyl, tetrazolyl, benzofuryl or benzofuranyl, isoquinolinyl, 1-oxoisoquinolin-2(1H)-yl, benzthiazolyl, xanthene, thioxanthene, phenothiazine, dihydroindole, benzo[1,3]dioxole, benzo[b]furyl, benzo[b]thiopheneyl, indazolyl, benzimidazolyl, 3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl, benzthiazolyl, puryl or purinyl, cinnolyl, quinolyl, quinazolyl, phthalazyl, quinazolyl, quinoxalyl, isoquinolyl, 4H-

[0005] quinolizyl, benzo-1,2,5-thiadiazolyl, or 1,8-naphthyridyl. Other examples of heteroaryls include 1,2,3,4-tetrahydroisoquinoline and 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine. Without limitation, monocyclic heteroaryls include furyl, thiophene-yl, 2H- pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, 1,3,4-thiadiazolyl, pyridyl, pyridazyl, pyrimidyl, pyrazolyl, pyrazyl, or 1,3,5-triazyl. Monocyclic heteroaryls are numbered according to standard chemical nomenclature. Without limitation, bicyclic heteroaryls include indolizyl, indolyl, isoindolyl, 3H- indolyl, indolinyl, benzo[b]furyl, benzo[b]thiopheneyl, quinolinyl, isoquinolinyl, indazolyl, benzimidazyl, benzthiazolyl, purinyl, 4H-quinolizyl, quinolyl, isoquinolyl, cinnolyl, phthalazyl, quinazolyl, quinoxalyl, 1,8-naphthyridyl, or pteridyl. Bicyclic heteroaryls are numbered according to standard chemical nomenclature. A heteroaryl is optionally substituted with one or more substituents such as aliphatic (e.g., alkyl, alkenyl, or alkynyl); cycloaliphatic; (cycloaliphatic)aliphatic; heterocycloaliphatic; (heterocycloaliphatic)aliphatic; aryl; heteroaryl; alkoxy; (cycloaliphatic)oxy; (heterocycloaliphatic)oxy; aryloxy; heteroaryloxy; (araliphatic)oxy; (heteroaraliphatic)oxy; aroyl; heteroaroyl; amino; oxo (on a non-aromatic carbocyclic or heterocyclic ring of a bicyclic or tricyclic heteroaryl); carboxy; amido; acyl (e.g., (aliphatic)carbonyl; (cycloaliphatic)carbonyl; ((cycloaliphatic)aliphatic)carbonyl; (araliphatic)carbonyl; (heterocycloaliphatic)carbonyl; ((heterocycloaliphatic)aliphatic)carbonyl; or (heteroaraliphatic)carbonyl); sulfonyl (e.g., aliphaticsulfonyl or aminosulfonyl); sulfinyl (e.g., aliphaticsulfinyl); sulfanyl (e.g., aliphaticsulfanyl); nitro; cyano; halo; hydroxy; mercapto; sulfoxy; urea; thiourea; sulfamoyl; sulfamide; or carbamoyl. Alternatively, a heteroaryl can be unsubstituted. Non-limiting examples of substituted heteroaryls include (halo)heteroaryl (e.g., mono- and di-(halo)heteroaryl); (carboxy)heteroaryl (e.g., (alkoxycarbonyl)heteroaryl); cyanoheteroaryl; aminoheteroaryl (e.g., ((alkylsulfonyl)amino)heteroaryl and ((dialkyl)amino)heteroaryl); (amido)heteroaryl (e.g., aminocarbonylheteroaryl, ((alkylcarbonyl)amino)heteroaryl, ((((alkyl)amino)alkyl)aminocarbonyl)heteroaryl, (((heteroaryl)amino)carbonyl)heteroaryl, ((heterocycloaliphatic)carbonyl)heteroaryl, and ((alkylcarbonyl)amino)heteroaryl); (cyanoalkyl)heteroaryl; (alkoxy)heteroaryl; - 23 - 1103012070\6\AMERICAS (sulfamoyl)heteroaryl (e.g., (aminosulfonyl)heteroaryl); (sulfonyl)heteroaryl (e.g., (alkylsulfonyl)heteroaryl); (hydroxyalkyl)heteroaryl; (alkoxyalkyl)heteroaryl; (hydroxy)heteroaryl; ((carboxy)alkyl)heteroaryl; (((dialkyl)amino)alkyl)heteroaryl; (heterocycloaliphatic)heteroaryl; (cycloaliphatic)heteroaryl; (nitroalkyl)heteroaryl; (((alkylsulfonyl)amino)alkyl)heteroaryl; ((alkylsulfonyl)alkyl)heteroaryl; (cyanoalkyl)heteroaryl; (acyl)heteroaryl (e.g., (alkylcarbonyl)heteroaryl); (alkyl)heteroaryl; or (haloalkyl)heteroaryl (e.g., trihaloalkylheteroaryl). As used herein, a “heteroaraliphatic” (such as a heteroaralkyl group) refers to an aliphatic group (e.g., a C1-4alkyl group) that is substituted with a heteroaryl group. “Aliphatic,” “alkyl,” and “heteroaryl” have been defined above. As used herein, “arylalkyl” refers to a monovalent moiety that is a radical of an alkyl compound, wherein the alkyl compound is substituted with an aromatic substituent (i.e., the aromatic compound includes a single bond to an alkyl group and wherein the radical is localized on the alkyl group). An arylalkyl group bonds to the illustrated chemical structure via the alkyl group. An arylalkyl can be represented by the structure, for example, , , , , or , wherein B is an aromatic moiety, for example, aryl or phenyl. Arylalkyl is optionally substituted (i.e., the aryl group and / or the alkyl group, can be substituted as disclosed herein). Examples of arylalkyl include, but are not limited to, benzyl. As used herein, a “heteroaralkyl” group refers to an alkyl group (e.g., a C1-4 alkyl group) that is substituted with a heteroaryl group. Both “alkyl” and “heteroaryl” have been defined above. A heteroaralkyl is optionally substituted with one or more substituents such as alkyl (including carboxyalkyl, hydroxyalkyl, and haloalkyl such as trifluoromethyl), alkenyl, alkynyl, cycloalkyl, (cycloalkyl)alkyl, heterocycloalkyl, (heterocycloalkyl)alkyl, aryl, heteroaryl, alkoxy, cycloalkyloxy, heterocycloalkyloxy, aryloxy, heteroaryloxy, aralkyloxy, heteroaralkyloxy, aroyl, heteroaroyl, nitro, carboxy, alkoxycarbonyl, alkylcarbonyloxy, aminocarbonyl, alkylcarbonylamino, cycloalkylcarbonylamino, (cycloalkylalkyl)carbonylamino, arylcarbonylamino, aralkylcarbonylamino, (heterocycloalkyl)carbonylamino, (heterocycloalkylalkyl)carbonylamino, heteroarylcarbonylamino, heteroaralkylcarbonylamino, cyano, halo, hydroxy, acyl, mercapto, alkylsulfanyl, sulfoxy, urea, thiourea, sulfamoyl, sulfamide, oxo, or carbamoyl. As used herein, “cyclic moiety” and “cyclic group” refer to mono-, bi-, and tri- cyclic ring systems including cycloaliphatic, heterocycloaliphatic, aryl, or heteroaryl, each of which has been previously defined. As used herein, a “bridged bicyclic ring system” refers to a bicyclic heterocyclicalipahtic (or heterocycloaliphatic) ring system or bicyclic cycloaliphatic ring system in which the rings are bridged. Examples of bridged bicyclic ring systems include, but are not limited to, adamantanyl, norbornanyl, bicyclo[3.2.1]octyl, bicyclo[2.2.2]octyl, bicyclo[3.3.1]nonyl, bicyclo[3.3.2]decyl, 2-oxabicyclo[2.2.2]octyl, 1-azabicyclo[2.2.2]octyl, 3-azabicyclo[3.2.1]octyl, and 2,6-dioxa-tricyclo[3.3.1.03,7]nonyl. A bridged bicyclic ring system can be optionally substituted with one or more substituents such as alkyl (including carboxyalkyl, hydroxyalkyl, and haloalkyl such as trifluoromethyl), alkenyl, alkynyl, cycloalkyl, (cycloalkyl)alkyl, heterocycloalkyl, (heterocycloalkyl)alkyl, aryl, heteroaryl, alkoxy, cycloalkyloxy, heterocycloalkyloxy, aryloxy, heteroaryloxy, aralkyloxy, heteroaralkyloxy, aroyl, heteroaroyl, nitro, carboxy, alkoxycarbonyl, alkylcarbonyloxy, aminocarbonyl, alkylcarbonylamino, cycloalkylcarbonylamino, (cycloalkylalkyl)carbonylamino, arylcarbonylamino, aralkylcarbonylamino, (heterocycloalkyl)carbonylamino, (heterocycloalkylalkyl)carbonylamino, heteroarylcarbonylamino, heteroaralkylcarbonylamino, cyano, halo, hydroxy, acyl, mercapto, alkylsulfanyl, sulfoxy, urea, thiourea, sulfamoyl, sulfamide, oxo, or carbamoyl. As used herein, an “acyl” group refers to a RX-C(O)- (such as alkyl-C(O)-, also referred to as “alkylcarbonyl”) where RXand “alkyl” have been defined previously. Acetyl and pivaloyl are examples of acyl groups. As used herein, an “aroyl” or “heteroaroyl” refers to an aryl-C(O)- or a heteroaryl-C(O)-. The aryl and heteroaryl portion of the aroyl or heteroaroyl is optionally substituted as previously defined herein. For example, aroyl includes benzoyl. As used herein, an “alkoxy” group refers to an alkyl-O- group where “alkyl” has been defined previously herein. As used herein, “haloalkoxy” refers to alkoxy, as defined above, wherein the alkoxy includes at least one substituent selected from a halogen (e.g., F, Cl, Br, or I). As used herein, a “carbamoyl” group refers to a group having the formula -O-CO-NRXRYor -NRX-CO-O-RZ, wherein RXand RYhave been defined above and RZcan be aliphatic, aryl, araliphatic, heterocycloaliphatic, heteroaryl, or heteroaraliphatic. As used herein, a “carboxy” group refers to –COOH, when used as a terminal group; or -OC(O)-, or -C(O)O- when used as an internal group. As used herein, an “ester” refers to –COORXwhen used as a terminal group; or –COORX– when used as an internal group, wherein RXhas been defined above. As used herein, an “alkoxycarbonyl,” which is encompassed by the term ester, used alone or in connection with another group refers to a group such as alkyl-O-C(O)- (i.e., a carbonate ester). As used herein, a “formate” refers to –OC(O)H. As used herein, an “acetate” refers to -OC(O)RX, wherein RXhas been defined above. In one embodiment, acetate is -OC(O)Me As used herein, a “haloaliphatic” or “haloalkyl” group refers to an aliphatic or alkyl group substituted with one to three halogen atoms. For instance, haloalkyl includes -CF3. As used herein, a “mercapto” or “sulfhydryl” group refers to -SH. As used herein, a “sulfo” group refers to -SO3H, or -SO3RXwhen used terminally or -S(O)3- when used internally. In one embodiment, -SO3H is a sulfonic acid. In one embodiment, RXSO3- is a sulfonate. As used herein, a “sulfamide” group refers to the formula -NRX-S(O)2-NRYRZwhen used terminally and -NRX-S(O)2-NRY- when used internally, wherein RX, RY, and RZhave been defined above. As used herein, a “sulfamoyl” group refers to the formula -S(O)2-NRYRZwherein RY, and RZhave been defined above. In one embodiment, -O-S(O)2-NRYRZis a sulfamate. As used herein, a “sulfonamide” group refers to the formula RZ-S(O)2-NRXRYor - NRX-S(O)2-RZwhen used terminally; or -S(O)2-NRX-, or -NRX-S(O)2- when used internally, wherein RX, RY, and RZare defined above. As used herein a “sulfide” group refers to -S-RXwhen used terminally and -S- when used internally, wherein RXhas been defined above. Examples of sulfanyls include aliphatic-S-, cycloaliphatic-S-, aryl-S-, or the like. As used herein a “sulfinyl” group refers to -S(O)-RXwhen used terminally and -S(O)- when used internally, wherein RXhas been defined above. Examples of sulfinyl groups include aliphatic-S(O)-, aryl-S(O)-, (cycloaliphatic(aliphatic))-S(O)-, cycloalkyl-S(O)-, heterocycloaliphatic-S(O)-, heteroaryl-S(O)-, and / or the like. As used herein, a “sulfonyl” group refers to -S(O)2-RXwhen used terminally and - S(O)2- when used internally, wherein RXhas been defined above. Examples of sulfonyl groups include aliphatic-S(O)2-, aryl-S(O)2-, (cycloaliphatic(aliphatic))-S(O)2-, cycloaliphatic-S(O)2-, heterocycloaliphatic-S(O)2-, heteroaryl-S(O)2-, (cycloaliphatic(amido(aliphatic)))-S(O)2-, and / or the like. As used herein, a “sulfinate” group refers to -O-S(O)-RX, or -S(O)-O-RX, when used terminally and -O-S(O)- or -S(O)-O- when used internally, where RXhas been defined above. As used herein, a “halogen” or “halo” group refers to fluorine (F), chlorine (Cl), bromine (Br), or iodine (I). As used herein, an “alkoxyalkyl” refers to an alkyl group modified with an alkoxy group, such as alkyl-O-alkyl- or ethers, wherein alkyl has been defined above. As used herein, a “carbonyl” or “oxo” refers to -C(O)- or =O. As used herein, the term “phospho” refers to phosphinates, phosphonates, phosphine oxides, phosphoramidates, phosphinic amides, and phosphonamidates. Examples of phosphinates, phosphonates, phosphine oxides, phosphoramidates, phosphinic amides, and phosphonamidates include -P(O)(RP)2, (RP)2P(O)ORP, and RP-PO(ORP)2, wherein RPis aliphatic, alkoxy, aryloxy, heteroaryloxy, (cycloaliphatic)oxy, (heterocycloaliphatic)oxy, aryl, heteroaryl, cycloaliphatic, or amino. As used herein, an “aminoalkyl” refers to the formula (RX)2N-alkyl- where RXhas been defined above. As used herein, a “cyanoalkyl” refers to the formula (NC)-alkyl-. As used herein, a “urea” group refers to the formula -NRX-CO-NRYRZand a “thiourea” refers to the formula -NRX-CS-NRYRZeach when used terminally and -NRX-CO-NRY- or -NRX-CS-NRY- each when used internally, wherein RX, RY, and RZhave been defined above. As used herein, a “guanidine” group refers to the formula -N=C(N(RXRY))(N(RXRY)) or -NRX-C(=NRX)NRXRYwherein RXand RYhave been defined above. As used herein, the term “amidino” group refers to the formula -C(NRX)NRXRYwherein RXand RYhave been defined above. As used herein, the term “vicinal” generally refers to the placement of substituents on a group that includes two or more carbon atoms, wherein the substituents are attached to adjacent carbon atoms. As used herein, the term “geminal” generally refers to the placement of substituents on the same carbon atom. As used herein, an “aliphatic chain” refers to a branched or straight aliphatic group (e.g., alkyl groups, alkenyl groups, or alkynyl groups). A straight aliphatic chain has the structure -[CH2]v-, where v is one to twelve. A branched aliphatic chain is a straight aliphatic chain that is substituted with one or more aliphatic groups. A branched aliphatic chain has the structure -[CQQ]v-, where each Q is independently a hydrogen (H or –H) or an aliphatic group; however, Q shall be an aliphatic group in at least one instance. The term aliphatic chain includes alkyl chains, alkenyl chains, and alkynyl chains, where alkyl, alkenyl, and alkynyl are defined above. The phrase “optionally substituted” is used interchangeably herein with the phrase “substituted or unsubstituted.” As described herein, compounds herein can be optionally substituted with one or more substituents, as illustrated generally above, or as exemplified by particular classes, subclasses, and species within this description. As described herein, variables R, X, L, Z, and other variables contained in any formulae described herein encompass specific groups, for example, alkyl and aryl. Unless otherwise noted, each of the specific groups within the variables R, X, L, and Z, and other variables contained therein can be optionally substituted with one or more substituents described herein. Each substituent of a specific group is further optionally substituted with one to three halo, cyano, oxo, alkoxy, hydroxy, amino, nitro, aryl, cycloaliphatic, heterocycloaliphatic, heteroaryl, haloalkyl, and / or alkyl. For instance, an alkyl group can be substituted with alkylsulfanyl and the alkylsulfanyl can be optionally substituted with one to three halo, cyano, oxo, alkoxy, hydroxy, amino, nitro, aryl, haloalkyl, and alkyl. As an additional example, the cycloalkyl portion of a (cycloalkyl)carbonylamino can be optionally substituted with one to three halo, cyano, alkoxy, hydroxy, nitro, haloalkyl, and alkyl. When two alkoxy groups are bound to the same atom or adjacent atoms, the two alkoxy groups can form a ring together with the atom(s) to which they are bound. As used herein, the term “substituted,” whether preceded by the term “optionally” or not, refers generally to the replacement of one or more hydrogen atoms in a given chemical structure with the radical of a specified substituent. Specific substituents are defined above and described below within the compounds and examples thereof. Unless otherwise indicated, an optionally substituted group can have a substituent at each substitutable position of the group, and when more than one position in any given structure can be substituted with more than one substituent selected from a specified group, the substituent can be either the same or different at every position. A ring substituent, such as a heterocycloalkyl, can be bound to another ring, such as a cycloalkyl, to form a spiro-bicyclic ring system, for example, both rings share one common atom. Non-limiting examples of spiro heterocycloalkyls include ; ; ; ; and . Spiro compounds depicted with overlapping rings indicate that the spirocyclic rings can bond at any vertex. For instance, in the spiro group , the two rings can bond at any of the three available vertex atoms in either ring. As one of ordinary skill in the art will recognize, combinations of substituents envisioned by this description are those combinations that result in the formation of stable or chemically feasible compounds. As used herein, “amino acid side chain” refers to the additional chemical moiety on the same carbon that bears a primary or secondary amine and a carboxylic acid of an amino acid. As would be appreciated by a person of skill in the art, there are twenty-one “standard” amino acids. Exemplary “standard” amino acids include, without limitation, alanine, serine, proline, arginine, and aspartic acid. Other amino acids include, cysteine, selenocysteine, and glycine (e.g., wherein the additional chemical moiety on the same carbon that bears the primary amine and carboxylic acid of glycine is hydrogen). Exemplary amino acid side chains include, without limitation, methyl (i.e., alanine), sec-buytl (i.e., isoleucine), iso-butyl (i.e., leucine), –CH2CH2SCH3(i.e., methionine), –CH2Ph (i.e., phenylalanine), (i.e., tryptophan), (i.e., tyrosine), iso-propyl (i.e., valine), hydroxymethyl (i.e., serine), –CH(OH)CH3(i.e., threonine), –CH2C(O)NH2(i.e., asparagine), –CH2CH2C(O)NH2(i.e., glutamine), –CH2SH (i.e., cysteine), –CH2SeH (i.e., selenocysteine), –CH2NH2(i.e., glycine), propylene or -CH2CH2CH2- (i.e., proline), –CH2CH2CH2NHC(=NH)NH2(i.e., arginine), (i.e., histidine), –CH2CH2CH2CH2NH2(i.e., lysine), –CH2COOH (i.e., aspartic acid), and –CH2CH2COOH (i.e., glutamic acid). As used herein, the phrase “stable or chemically feasible” refers to compounds that are not substantially altered when subjected to conditions to allow for their production, detection, recovery, purification, and / or use for one or more of the purposes disclosed herein. In some embodiments, a stable compound or chemically feasible compound is one that is not substantially altered when kept at a temperature of 40 °C or less, in the absence of moisture or other chemically reactive conditions, for at least a week. As used herein, an “effective amount” is defined as the amount required to confer a therapeutic effect on the treated subject or patient, and is typically determined based on age, surface area, weight, and / or condition of the subject or patient. The interrelationship between dosages for animals and humans (based on milligrams per meter squared of body surface) is described by Freireich et al., Cancer Chemother. Rep., 50: 219 (1966). Body surface area may be approximately determined from height and weight of the subject or patient. See, e.g., Scientific Tables, Geigy Pharmaceuticals, Ardsley, New York, 537 (1970). As used herein, “patient” refers to an animal, alternatively a mammal, including a human. The terms “pharmaceutical formulation” and “pharmaceutical composition” refer to preparations that are in such form as to permit the biological activity of the active ingredient to be effective, and that contain no additional components that are unacceptably toxic to an individual or subject to which the formulation or composition would be administered. Such formulations or compositions may be sterile. The term “excipients” as used herein includes pharmaceutically acceptable excipients, carriers, vehicles, or stabilizers that are nontoxic to the subject, cell, or mammal being exposed thereto at the dosages and concentrations employed. In certain embodiments, the physiologically acceptable excipient is an aqueous pH buffered solution. The terms “treating” or “treatment” of a disease refer to executing a protocol, which may include administering one or more therapeutic agent to a subject and / or an individual (human or otherwise), in an effort to obtain beneficial or desired results in the subject or individual, including clinical results. In certain embodiments, beneficial or desired clinical results include, but are not limited to, alleviation or amelioration of one or more symptoms, diminishment of extent of disease, stabilized (i.e., not worsening) state of disease, preventing spread of disease, delay or slowing of disease progression, amelioration or palliation of the disease state, and remission (whether partial or total). In certain embodiments, “treatment” can also mean prolonging survival as compared to expected survival of an individual not receiving treatment. In certain embodiments, “treating” and “treatment” may occur by administration of one dose of a therapeutic agent or therapeutic agents, or may occur upon administration of a series of doses of a therapeutic agent or therapeutic agents. In certain embodiments, “treating” or “treatment” does not require complete alleviation of signs or symptoms, and does not require a cure. In certain embodiments, “treatment” can also refer to clinical intervention, such as administering one or more therapeutic agents to a subject and / or an individual, designed to alter the natural course of the subject, individual, or cell being treated (i.e., to alter the course of the individual or cell that would occur in the absence of the clinical intervention). In certain embodiments, the term “therapeutic agent” can refer to a compound or drug that induces or modulates KLHDC1 or KLHDC2 activity, or compositions thereof. The term “individual,” “patient,” or “subject” refers to a mammal. In certain embodiments, a “mammal” for purposes of treatment includes humans; non-human primates; domestic and farm animals; and zoo, sports, or pet animals, such as dogs, horses, rabbits, cattle, pigs, hamsters, gerbils, mice, ferrets, rats, cats, etc. In some embodiments, the individual or subject is human. As used herein, the term “about” means within ± 10% of a stated value. For example, a dose that is about 100 mg / kg provides that the dose can be 90 mg / kg to 110 mg / kg. By way of further example, an amount of an additional therapeutic agent ranging from about 50% to about 100% provides that the amount of additional therapeutic agent ranges from 45-55% to 90- 110%. A person of skill in the art will appreciate the scope and application of the term “about” when used to describe other stated values disclosed herein. Unless otherwise stated, structures depicted herein also are meant to include all isomeric (e.g., enantiomeric, diastereomeric, and geometric (or conformational)) forms of the chemical structure; for example, the (R)- and (S)- configurations for each asymmetric center, (Z)- and (E)- double bond isomers, and syn- / cis- and anti- / trans-conformational isomers. Therefore, single stereochemical isomers as well as enantiomeric, diastereomeric, and geometric (or conformational) mixtures of the present compounds are within the scope of the description. Alternatively, as used herein, “enantiomeric excess (ee)” refers to a dimensionless mol ratio describing the purity of chiral substances that contain, for example, a single stereogenic center. For instance, an enantiomeric excess of zero would indicate a racemic (e.g., 50:50 mixture of enantiomers, or no excess of one enantiomer over the other). By way of further example, an enantiomeric excess of ninety-nine would indicate a nearly stereopure enantiomeric compound (i.e., large excess of one enantiomer over the other). The percentage enantiomeric excess, % ee = ([(R)-compound]-[(S)-compound]) / ([(R)-compound]+[(S)-compound]) x 100, where the (R)- compound > (S)-compound; or % ee = ([(S)-compound]-[(R)-compound]) / ([(S)-compound]+[(R)- compound]) x 100, where the (S)-compound > (R)-compound. Also as used herein, “diastereomeric excess (de)” refers to a dimensionless mol ratio describing the purity of chiral substances that contain more than one stereogenic center. For example, a diastereomeric excess of zero would indicate an equimolar mixture of diastereoisomers. By way of further example, diastereomeric excess of ninety-nine would indicate a nearly stereopure diastereomeric compound (i.e., large excess of one diastereomer over the other). Diastereomeric excess may be calculated via a similar method to ee. As would be appreciated by a person of skill, de is usually reported as percent de (% de). % de may be calculated in a similar manner to % ee. In certain embodiments, the compounds or inhibitors described herein have an ee, de, % ee, or % de greater than zero. For example, in certain embodments, the compounds or inhibitors described herein have an ee, de, % ee, or % de of ten. In certain embodiments, the compounds or inhibitors described herein have an ee, de, % ee, or % de of twenty-five. In certain embodiments, the compounds or inhibitors described herein have an ee, de, % ee, or % de of fifty. In certain embodiments, the compounds or inhibitors described herein have an ee, de, % ee, or % de of seventy-five. In certain embodiments, the compounds or inhibitors described herein have an ee, de, % ee, or % de of ninety-nine. In certain embodiments, the compounds or inhibitors described herein have an ee, de, % ee, or % de range from ninety to one hundred. In certain embodiments, the compounds or inhibitors described herein have an ee, de, % ee, or % de range from ninety-five to one hundred. In certain embodiments, the compounds or inhibitors described herein have an ee, de, % ee, or % de range from ninety-seven to one hundred. In certain embodiments, the compounds or inhibitors described herein have an ee, de, % ee, or % de range from ninety-eight to one hundred. In certain embodiments, the compounds or inhibitors described herein have an ee, de, % ee, or % de range from ninety-nine to one hundred. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is one. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is two. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is three. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is four. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is five. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is six. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is seven. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is eight. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is nine. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is ten. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is eleven. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is twelve. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is thirteen. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is fourteen. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is fifteen. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is sixteen. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is seventeen. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is eighteen. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is nineteen. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is twenty. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is twenty-one. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is twenty-two. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is twenty-three. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is twenty-four. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is twenty-five. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is twenty-six. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is twenty-seven. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is twenty-eight. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is twenty-nine. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is thirty. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is thirty-one. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is thirty-two. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is thirty- three. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is thirty-four. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is thirty-five. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is thirty-six. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is thirty-seven. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is thirty-eight. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is thirty-nine. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is forty. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is forty-one. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is forty-two. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is forty-three. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is forty-four. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is forty-five. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is forty- six. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is forty-seven. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is forty-eight. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is forty-nine. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is fifty. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is fifty-one. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is fifty-two. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is fifty-three. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is fifty-four. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is fifty-five. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is fifty-six. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is fifty-seven. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is fifty-eight. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is fifty-nine. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is sixty. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is sixty- one. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is sixty-two. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is sixty-three. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is sixty-four. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is sixty-five. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is sixty-six. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is sixty-seven. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is sixty-eight. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is sixty-nine. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is seventy. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is seventy-one. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is seventy-two. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is seventy-three. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is seventy-four. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is seventy-five. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is seventy-six. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is seventy-seven. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is seventy-eight. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is seventy-nine. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is eighty. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is eighty-one. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is eighty-two. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is eighty- three. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is eighty-four. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is eighty-five. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is eighty-six. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is eighty-seven. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is eighty-eight. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is eighty-nine. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is ninety. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is ninety-one. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is ninety-two. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is ninety-three. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is ninety-four. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is ninety- five. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is ninety-six. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is ninety-seven. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is ninety-eight. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is ninety-nine. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is one hundred. In certain embodiments, compounds or inhibitors described within Table 1 herein have an ee, de, % ee, or % de as described within this paragraph. In certain embodiments, compounds or inhibitors described in the Examples and / or Biological Examples have an ee, de, % ee, or % de as described within this paragraph. Unless otherwise stated, all tautomeric forms of the compounds of this description are within the scope of this description. Additionally, unless otherwise stated, structures depicted herein also are meant to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structures except for the replacement of hydrogen by deuterium or tritium, or the replacement of a carbon by a13C- or14C-enriched carbon are within the scope of this description. Such compounds are useful, for example, as analytical tools or probes in biological assays, or as therapeutic agents. As used herein, the term “&1” means that a compound including the “&1” notation at a particular chemical element or atom (e.g., carbon) within the compound was prepared as a mixture of two stereoisomers at the noted chemical element or atom (e.g., a diastereomeric mixture having a de or % de as described above). Chemical structures and nomenclature are derived from ChemDraw, version 23.1, Cambridge, MA. It is noted that the use of the descriptors “first,” “second,” “third,” or the like is used to differentiate separate elements (e.g., solvents, reaction steps, processes, reagents, or the like) and may or may not refer to the relative order or relative chronology of the elements described. Compounds In certain embodiments, provided herein is a compound having the following formula wherein is ; R3, when present, is ; and R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl, –C(O)-heteroalkylene-NR4aR4b, alkyl, –C(O)-alkylene-COOR5, –C(O)-alkylene-C(O)NR4aR4b, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl, wherein R4aand R4bare independently hydrogen, alkyl, or acyl. In one embodiment, R3ais alkyl; R3bis hydrogen; and R3cis one or more alkoxy or halo. In one embodiment, R3is , , , , or . In one embodiment, R3is . In one embodiment, R3is . In one embodiment, R3is . In one , R3is embodiment, R3is e embodi en presen a th mbered heterocycloalk t one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl. In one

[0006] embodiment, R4is , , , , or . In bodiment, R is . In one embodiment, R is . In one embodiment, R4is . In one e bod et,4is . In one embodiment, R4is . In one embodiment, R1is . In certain embodiments, the compound is selected fro g onsisting of (2-(3-(1-acetylazetidin-3-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (1), N-(2-((2H-tetrazol-5-yl)amino)-2-oxoethyl)-2-(3-(1-acetylpiperidin- 4-yl)-5'-fluoro-1'- , N-((2H-tetrazol-5- yl)methyl)-2-(2-(3 4,6'-biindazol]-1- yl)acetamido)acet -1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)-N e (4), N-((2-(3-(1- acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycyl)N methy e (5), N-((2H-tetrazol-5-y -(2-(2-(3-(1-acetylpiperidin luoro-1'- methy H-[4,6'-biindazol]-1-yl)ace amido)acetamide (6), (2-(3-(1- acety n-4-yl)-5'-fluoro-1'-methyl 6'-biindazol]-1-yl)acetyl)-N ycyl)- N-me ygyine (7) N(2-((5H-tetrazol5yl)amino)-2-oxoethyl)-2-(3-(1-ace in-4-yl)- 5'-fluoro-1'-methyl H-[4,6'-biindazol]-1-yl)-N-methylacetamide (8), (2-(5'-fluoro-1'-methyl- 3-(piperidin-4-yl)- [4,6'-biindazol]-1-yl)acetyl e (76), (2-(3-(1- acetylpiperidin-4-y uoro-1'-methyl-1H,1'H-[4,6 yl)acetyl)glycylglycine (9), N-(2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N- methylglycylglycine (10), (2-(3-(1-acetylpiperidin-4-yl)-4-(5-fluoro-1-methyl-1H-indazol-6-yl)- 1H-pyrazolo[3,4-b]pyridin-1-yl)acetyl)glycylglycine (11), rac-(R)-(R)-(2-(3-(1-acetylazepan-4- yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (12), N-(2-(3-(1- acetylazetidin-3-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N- methylglycylglycine (13), (2-(3-(4-acetylpiperazin-1-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)acetyl)glycylglycine (14), (2-(3-(1-acetylpiperidin-4-yl)-5'-methoxy-1'-methyl- 1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (15), (2-(3-(1-acetylpiperidin-4-yl)-7'-fluoro-1'- methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (16), methyl (2-(5'-fluoro-1'-methyl-3- (piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (215), tert-butyl (2-(5'- fluoro-1'-methyl-3-(piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (216), methyl (2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (217), (2-(3-(1-acetylpiperidin-4-yl)-5',7'-difluoro-1'-methyl-1H,1'H- [4,6'-biindazol]-1-yl)acetyl)glycylglycine (218), and (2-(3-(1-acetylpiperidin-4-yl)-4'-fluoro-1'- methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (17). In one embodiment, the compound is (2-(3-(1-acetylazetidin-3-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (1). In one embodiment, the compound is N-(2-((2H-tetrazol-5-yl)amino)- 2-oxoethyl)-2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetamide (2). In one embodiment, the compound is N-((2H-tetrazol-5-yl)methyl)-2-(2-(3-(1- acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)acetamide (3). In one embodiment, the compound is 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H- [4,6'-biindazol]-1-yl)-N-(2-((2-amino-2-oxoethyl)amino)-2-oxoethyl)acetamide (4). In one embodiment, the compound is N-((2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)acetyl)glycyl)-N-methylglycine (5). In one embodiment, the compound is N-((2H- tetrazol-5-yl)methyl)-2-(2-(2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)acetamido)acetamido)acetamide (6). In one embodiment, the compound is N-(N- (2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N- methylglycyl)-N-methylglycine (7). In one embodiment, the compound is N-(2-((5H-tetrazol-5- yl)amino)-2-oxoethyl)-2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]- 1-yl)-N-methylacetamide (8). In one embodiment, the compound is (2-(5'-fluoro-1'-methyl-3- (piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (76). In one embodiment, the compound is (2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (9). In one embodiment, the compound is N-(2-(3-(1-acetylpiperidin-4-yl)- 5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N-methylglycylglycine (10). In one embodiment, the compound is (2-(3-(1-acetylpiperidin-4-yl)-4-(5-fluoro-1-methyl-1H-indazol-6- yl)-1H-pyrazolo[3,4-b]pyridin-1-yl)acetyl)glycylglycine (11). In one embodiment, the compound is rac-(R)-(R)-(2-(3-(1-acetylazepan-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (12). In one embodiment, the compound is N-(2-(3-(1-acetylazetidin-3- yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N-methylglycylglycine (13). In one embodiment, the compound is (2-(3-(4-acetylpiperazin-1-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)acetyl)glycylglycine (14). In one embodiment, the compound is (2-(3-(1- acetylpiperidin-4-yl)-5'-methoxy-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (15). In one embodiment, the compound is (2-(3-(1-acetylpiperidin-4-yl)-7'-fluoro-1'-methyl- 1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (16). In one embodiment, the compound is methyl (2-(5'-fluoro-1'-methyl-3-(piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (215). In one embodiment, the compound is tert-butyl (2-(5'-fluoro-1'- methyl-3-(piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (216). In one embodiment, the compound is methyl (2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H- [4,6'-biindazol]-1-yl)acetyl)glycylglycinate (217). In one embodiment, the compound is (2-(3-(1- acetylpiperidin-4-yl)-5',7'-difluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (218). In one embodiment, the compound is (2-(3-(1-acetylpiperidin-4-yl)-4'-fluoro-1'-methyl- 1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (17). In certain embodiments, R1is . In certain embodiments, the compound is selected from the group consisting of 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(4- (hydroxymethyl)-2-methylthiophen-3-yl)acetamide (18), 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro- 1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(1,6-naphthyridin-4-yl)acetamide (19), 2-(3-(1- acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(isoquinolin-4- yl)acetamide (20), 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)-N-(3-methylisoxazol-4-yl)acetamide (21), 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl- 1H,1'H-[4,6'-biindazol]-1-yl)-N-(1,7-naphthyridin-4-yl)acetamide (22), 2-(3-(1-acetylpiperidin-4- yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(5-methylpyridin-3-yl)acetamide (23), 2- (3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(4-methylpyridin- 3-yl)acetamide (24), 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)-N-(7-hydroxy-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)acetamide (25), 2-(3-(1- acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(pyrazolo[1,5- a]pyridin-4-yl)acetamide (26), 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)-N-(pyrazolo[1,5-b]pyridazin-3-yl)acetamide (27), 2-(3-(1-acetylpiperidin-4-yl)- 5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(benzo[d][1,3]dioxol-4-yl)acetamide (28), 2- (3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(2-(2- methoxyethoxy)ethyl)acetamide (29), 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H- [4,6'-biindazol]-1-yl)-N-(2-(methoxymethy -triazol-4-yl)acetamide (30), N-(4-(1H- pyrazol-1-yl)pyrimidin-5-yl)-2-(3-(1-acetyl -yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)acetamide (31), 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)-N-(1-(pyridazin-3-yl)-1H-pyrazol-5-yl)acetamide (32), 2-(3-(1-acetylpiperidin- 4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(pyrido[3,4-b]pyrazin-8-yl)acetamide (33), 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(2,7- naphthyridin-4-yl)acetamide (34), N-([1,2,4]triazolo[1,5-a]pyridin-8-yl)-2-(3-(1-acetylpiperidin- 4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetamide (35), and 2-(3-(1- acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(3-cyano-2- methylphenyl)acetamide (36). In one embodiment, the compound is 2-(3-(1-acetylpiperidin-4-yl)- 5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(4-(hydroxymethyl)-2-methylthiophen-3- yl)acetamide (18). In one embodiment, the compound is 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'- methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(1,6-naphthyridin-4-yl)acetamide (19). In one embodiment, the compound is 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)-N-(isoquinolin-4-yl)acetamide (20). In one embodiment, the compound is 2-(3- (1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(3-methylisoxazol- 4-yl)acetamide (21). In one embodiment, the compound is 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro- 1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(1,7-naphthyridin-4-yl)acetamide (22). In one embodiment, the compound is 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)-N-(5-methylpyridin-3-yl)acetamide (23). In one embodiment, the compound is 2- (3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(4-methylpyridin- 3-yl)acetamide (24). In one embodiment, the compound is 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro- 1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(7-hydroxy-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin- 6-yl)acetamide (25). In one embodiment, the compound is 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro- 1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(pyrazolo[1,5-a]pyridin-4-yl)acetamide (26). In one embodiment, the compound is 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)-N-(pyrazolo[1,5-b]pyridazin-3-yl)acetamide (27). In one embodiment, the compound is 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N- (benzo[d][1,3]dioxol-4-yl)acetamide (28). In one embodiment, the compound is 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H- [4,6'-biindazol]-1-yl)-N-(2-(2-methoxyethoxy)ethyl)acetamide (29). In one embodiment, the compound is 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N- (2-(methoxymethyl)-2H-1,2,3-triazol-4-yl)acetamide (30). In one embodiment, the compound is N-(4-(1H-pyrazol-1-yl)pyrimidin-5-yl)-2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H- [4,6'-biindazol]-1-yl)acetamide (31). In one embodiment, the compound is 2-(3-(1- acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(1-(pyridazin-3-yl)-1H- pyrazol-5-yl)acetamide (32). In one embodiment, the compound is 2-(3-(1-acetylpiperidin-4-yl)- 5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(pyrido[3,4-b]pyrazin-8-yl)acetamide (33). In one embodiment, the compound is 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H- [4,6'-biindazol]-1-yl)-N-(2,7-naphthyridin-4-yl)acetamide (34). In one embodiment, the compound is N-([1,2,4]triazolo[1,5-a]pyridin-8-yl)-2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'- methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetamide (35). In one embodiment, the compound is 2-(3- (1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(3-cyano-2- methylphenyl)acetamide (36). In certain embodiments, R1is . In certain embodiments, the compound is selected from the group consisting of (S)-2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl- 1H,1'H-[4,6'-biindazol]-1-yl)-N-(2-hydroxy-1-(5-methyl-1H-1,2,4-triazol-3-yl)ethyl)acetamide (37), (R)-2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-((3- (1-hydroxyethyl)-1H-1,2,4-triazol-5-yl)methyl)acetamide (38), 2-(3-(1-acetylpiperidin-4-yl)-5'- fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-((5-ethyloxazol-2-yl)methyl)acetamide (39), 2- (3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-((5- (difluoromethyl)-1,24-oxadiazol-3-yl)methyl)acetamide (40), 2-(3-(1-acetylpiperidin-4-yl)-5'- fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-((2-methoxypyrimidin-4-yl)methyl)acetamide (41), 3-((2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetamido)methyl)-1,2,4-oxadiazole-5-carboxamide (42), 2-(3-(1-acetylpiperidin-4-yl)-5'- fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-((5-hydroxy-6-methoxypyridin-2- yl)methyl)acetamide (43), and 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)-N-methyl-N-((5-methyl-1,2,4-oxadiazol-3-yl)methyl)acetamide (44). In one embodiment, the compound is (S)-2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)-N-(2-hydroxy-1-(5-methyl-1H-1,2,4-triazol-3-yl)ethyl)acetamide (37). In one embodiment, the compound is (R)-2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)-N-((3-(1-hydroxyethyl)-1H-1,2,4-triazol-5-yl)methyl)acetamide (38). In one embodiment, the compound is 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)-N-((5-ethyloxazol-2-yl)methyl)acetamide (39). In one embodiment, the compound is 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N- ((5-(difluoromethyl)-1,24-oxadiazol-3-yl)methyl)acetamide (40). In one embodiment, the compound is 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N- ((2-methoxypyrimidin-4-yl)methyl)acetamide (41). In one embodiment, the compound is 3-((2- (3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)methyl)- 1,2,4-oxadiazole-5-carboxamide (42). In one embodiment, the compound is 2-(3-(1- acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-((5-hydroxy-6- methoxypyridin-2-yl)methyl)acetamide (43). In one embodiment, the compound is 2-(3-(1- acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-methyl-N-((5-methyl- 1,2,4-oxadiazol-3-yl)methyl)acetamide (44).

[0007] In certain embodiments, R1is . In certain embodiments, R1is . In certain embodiments, R1is . In certain embodiments, R1is . In certain embodiments, R1is . In one embodiment, the compound is rac-2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)- N-((2R,3R)-2-(1-methyl-1H-imidazol-2-yl)tetrahydrofuran-3-yl)acetamide (45). In one embodiment, the compound is rac-2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)-N-methyl-N-(((2R,3R)-3-(3-methyl-1H-1,2,4-triazol-5-yl)tetrahydrofuran-2- yl)methyl)acetamide (46). In one embodiment, the compound is 2-(3-(1-acetylpiperidin-4-yl)-5'- fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-1-(3-(hydroxymethyl)-6,7-dihydro- [1,2,3]triazolo[1,5-a]pyrazin-5(4H)-yl)ethan-1-one (47). In one embodiment, the compound is N- ([1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-yl)-2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl- 1H,1'H-[4,6'-biindazol]-1-yl)acetamide (48). In one embodiment, the compound is 2-(3-(1- acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[46' bii d zol]-1-yl)-N-(1-methyl-4-oxo-1,4- dihydropyrimidin-2-yl)acetamide (49). In one emb he compound is N-(2-(2H-tetrazol-2- yl)ethyl)-2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1' H,1'H-[4,6'-biindazol]-1- yl)acetamide (50). n certain embodiments, prov compound having the following wherein is s alkyl; R3bis hydrogen; and R3cis cyano. In certain embodiments, R3is . In certain embodiments, R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl. In certain embodiments, R4is . In certain embodiments, R1is . In one embodiment, the compound is (2- (3-(1-acetylpiperidin-4-yl)-5'-cyano-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (51). In certain embodiments, provided herein is a compound having the following formula wherein is ; and R3ais alkyl; R3bis hydrogen; and R3cis chloro. In certain embodiments, R3In certain embodiments, R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl. In certain embodiments, R4is . In certain embodiments, R1is . In one embodiment, the compound is (2- (3-(1-acetylpiperidin-4-yl)-5'-chloro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (52). In certain embodiments, provided herein is a compound having the following formu wherein i ; and R3ais alkyl; R3bis hydrogen; and R3cis alkyl. In certain embodiments, R3is n certain embodiments, R4, when present, is a three- to eight-membered heterocycloa ng at least one nitrogen, wherein the at nitrogen is unsubstituted or su cyl. In certain embodiments, R4is . In certain embodiments, R1is . In one embodiment, the compound is (2-(3-(1- acetylpiperidin-4-yl)-1',5'-dimethyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (53). In certain embodiments, provided herein is a compound having the following formula wherei ; and R3is . In certain embodim , , hen present, is heterocycloalkyl, wherein heterocycloalkyl is unsubstituted or substituted with alkyl. In certain em R4is or . In certain embodiments, R1is . In one embodiment, the compound is (2-(5'-fluoro 3-morpholino-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (54) or (2-(3-((2 dimethylmorpholino)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (55). In one embodiment, the c 2-(5'-fluoro-1'-methyl-3-morpholino-1H,1'H-[4,6'- biindazol]-1-yl)acetyl)glycylg one embodiment, the compound is (2-(3-((2R,6S)- 2,6-dimethylmorpholino)-5'-fl 1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (55). In certain embodiments, provided herein is a compound having the following formula wherei i ; and R3i . In certain embodime ts, , w en prese , ydrogen, alkyl, haloalkyl, aryl, or arylalkyl. In certain embodiments, R4is hydrogen, methyl, ethyl, isopropyl, trifluoromethyl, phenyl, pyridyl, or benzyl. In certain embodiments, R1is . I , the compound is selected from onsisting of (2-(5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylgl N-(2-((2H-tetrazol-5-yl)amino)-2-oxoethyl)-2-(2-(5'-fluoro-1',3- dimethyl-1H,1'H- -1-yl)acetamido)acetamide (57), (2-(5'-fluoro-1',3-dimethyl- 1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (58), (2-(3-ethyl-5'-fluoro-1'-methyl-1H,1'H- [4,6'-biindazol]-1-yl)acetyl)glycylglycine (59), N-(2-((2H-tetrazol-5-yl)amino)-2-oxoethyl)-2-(2- (5'-fluoro-3-isopropyl-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)acetamide (60), (2-(5'- fluoro-3-isopropyl-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (61), (2-(5'- fluoro-1'-methyl-3-(trifluoromethyl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (62), N- (2-(5'-fluoro-1'-methyl-3-(trifluoromethyl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N- methylglycylglycine (63), N-(2-((2H-tetrazol-5-yl)amino)-2-oxoethyl)-2-(2-(5'-fluoro-1'-methyl- 3-(trifluoromethyl)-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)acetamide (64), (2-(5'-fluoro-1'- methyl-3-phenyl-1H,1'H-[4,6'-biindazol] 1 l) l) l cylglycine (65), (2-(5'-fluoro-1'-methyl- 3-(pyridi 1'H-[4,6'-biindazol] ylglycine (66 l-5'-fluoro-1'- methyl-1 biindazol]-1-yl)ace (67), (2 1-methyl-1H- indazol-6 azolo[4,3-c]pyridin ylglycine (6 4-(5-fluoro-1- methyl-1 -yl)-1H-pyrazolo[3 )acetyl)glycy ). In one embodiment, the compound is (2-(5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (56). In one embodiment, the compound is N-(2-((2H-tetrazol-5- yl)amino)-2-oxoethyl)-2-(2-(5'-fluoro-1' H,1'H-[4,6'-biindazol]-1- yl)acetamido)acetamide (57). In one em e compound is (2-(5'-fluoro-1',3-dimethyl- 1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glyc In one embodiment, the compound is (2- (3-ethyl-5'-fluoro-1'-methyl-1H,1'H-[4,6 yl)acetyl)glycylglycine (59). In one embodiment, the compound is N-(2-((2H-tetrazol-5-yl)amino)-2-oxoethyl)-2-(2-(5'-fluoro-3- isopropyl-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)acetamide (60). In one embodiment, the compound is (2-(5'-fluoro-3-isopropyl-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (61). In one embodiment, the compound is (2-(5'-fluoro-1'-methyl-3- (trifluoromethyl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (62). In one embodiment, the compound is N-(2-(5'-fluoro-1'-methyl-3-(trifluoromethyl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)- N-methylglycylglycine (63). In one embodiment, the compound is N-(2-((2H-tetrazol-5- yl)amino)-2-oxoethyl)-2-(2-(5'-fluoro-1'-methyl-3-(trifluoromethyl)-1H,1'H-[4,6'-biindazol]-1- yl)acetamido)acetamide (64). In one embodiment, the compound is (2-(5'-fluoro-1'-methyl-3- phenyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (65). In one embodiment, the compound is (2-(5'-fluoro-1'-methyl-3-(pyridin-3-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (66). In one embodiment, the compound is (2-(3-benzyl-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (67). In one embodiment, the compound is (2-(4-(5-fluoro-1-methyl-1H- indazol-6-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)acetyl)glycylglycine (68). In one embodiment, the compound is (2-(4-(5-fluoro-1-methyl-1H-indazol-6-yl)-1H-pyrazolo[3,4-c]pyridin-1- yl)acetyl)glycylglycine (69). In certain embodiments, provided herein is a compound having the following formula wherein is ; and R3is . In certain embodiments, R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with –C(O)-heteroalkylene-NR4aR4band wherein R4aand R4bare independently hydrogen, alkyl, or acyl. In certain embodiments, R4is . In certain embodiments, R1is . In certain embodiments, the compound is selected from the group consisting of methyl (2-(3-(1-(3-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)propanoyl)piperidin-4-yl)-5'-fluoro-1'- methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (70) and (2-(3-(1-(3-(2-(2-(2- aminoe thoxy)propanoy -fluoro-1'-methyl-1H,1'H-[4,6'- biindaz glycylglycine (7 ment, the co thyl (2-(3-(1- (3-(2-(2 xy)ethoxy)ethox din-4-yl)-5' hyl-1H,1'H- [4,6'-bii cetyl)gl yc embodiment d is (2-(3-(1- (3-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)propanoyl)piperidin-4-yl)-5' hyl-1H,1'H- [4,6'-biindazol]-1-yl)acetyl)glycylglycine (71). In certain embodiments, provided herein is a compound having the following formula wherein R3is . In certain embodiments, R4, when present, heterocycloalkyl comprising at least one nitrogen, wherein the ubstituted or substituted with –C(O)-alkylene-COOR5or –C wherein R4aand R4bare independently hydrogen, alkyl, or acyl. In certain embodiments, R4is or . In certain embodiments, R1is . In certain embodiments, the compound is selected from the group consisting of 4-(4-(1-(2-((2-((carboxymethyl)amino)-2- oxoethyl)amino)-2-oxoethyl)-4-(5-fluoro-1-methyl-1H-indazol-6-yl)-1H-pyrazolo[3,4-b]pyridin- 3-yl)piperidin-1-yl)-4-oxobutanoic acid (72), (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-4- (5-fluoro 1 methyl 1H-indazol-6-yl)-1 pyridin-1-yl)acetyl)glycylglycine (73), and (5'-fluoro-1'-met lamino)-4-ox peridin-4-yl)- 1H,1'H ]-1-yl)acetyl)gly . In one emb compound is 4-(4-(1 xymethyl)amino) )-2-oxoethyl) 1-methyl- 1H-indazol 6 yl) 1H pyrazolo[3,4-b]pyridin-3-yl)piperidin-1-yl)-4-oxo (72). In one embodiment, the compound is (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-4-(5-fluoro-1- methyl-1H-indazol-6-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl)acetyl)glycylglycine (73). In one embodiment, the compound is methyl (2-(5'-fluoro-1'-methyl-3-(1-(4-(methylamino)-4- oxobutanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycina In certain embodiments, provided herein is a compound hav lowing wherein is ; and R3is . In certain 4, when present, is –N(R5)C(O)-alkylene-NR4aR4bwherein R4aand R4bare drogen, alkyl, or acyl. In certain e R4is . In certain embodiments, R1is . In one embodiment, the compound is (2-(3-(3- acetamidopropanamido)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (74). In certain embodiments, provided herein is a compound having the following formula wherein is ; and R3is . In certain embodiments, R4, when present, is -alkylene-NR4aR4bwherein R4aand R4bare independently hydrogen, alkyl, or acyl. In certain embodiments, R4is . In certain embodiments, R1is . In one embodiment, the compound is (2-(3- yl)-5'-fluoro- 1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (75). In certa s, provided herein is a compound having the following formula wherein is ; and R3is . In certain embodiments, R4, when present, is three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl. In certain embod or ments, R1is . In certain embod mpound ecte g p onsisting o ro-1'-methyl-3- (piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (76) and (2-(5'-fluoro-1'- methyl-3-(1-methylpiperidin-4-yl)-1H,1'H-[4,6'-biinda l)glycylglycine (77). In one embodiment, the compound is (2-(5'-fluoro-1'-methyl- yl)-1H,1'H-[4,6'-biindazol]- 1-yl)acetyl)glycylglycine (76). In one embodiment, the 2-(5'-fluoro-1'-methyl-3-(1- methylpiperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)ace ne (77). rtain embodiments, provided herein is a compound having the following formula wherein is ; and R3is . In certain embodiments, R4, when present, is a five- to fifteen-membered spiro bicyclic heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl. In certain embodiments, the five- to fifteen-membered spiro bicyclic heterocy prising at least on rein n1is zero to six, n2is zero to three, and n3is one to three. In certain embodiments, R4is . In certain embodiments, R1In one embodiment, the compound is (2-(3-(2-acetyl-2- azaspiro[3.3]heptan-6-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (78) or N-(2-(3-(2-acetyl-2-azaspiro[3.3]heptan-6-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)acetyl)-N-methylglycylglycine (79). In one embodiment, the compound is (2-(3- (2-acetyl-2-azaspiro[3.3]heptan-6-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (78). In one embodiment, the compound is N-(2-(3-(2-acetyl-2- azaspiro[3.3]heptan-6-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N- methylglycylglycine (79). In certain embodiments, provided herein is a compound having the following formul wherein is ; and R3is . In certain embodiments, R4, when present, is –NR4aR4bwherein R4aand R4bare independently hydrogen, alkyl, aryl, heteroaryl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, or arylalkyl. In certain embodiments, R4is . In certain em is . In one embodiment, the compound is (2-(5'-fluoro-1'-methyl-3-(methyl(pheny 1H,1'H-[4,6'- biindazol]-1-yl)acetyl)glycylglycine (80). In certain embodiments, provided herein is a compound he following formula is ; and R3ais alkyl; R3bis hydrogen; and R3cis alkyl or hydrogen. In certain embodiments, R3is . In certain embodiments, R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl. In certain embodiments, R4is . In certain embodiments, R1is . In certain embodiments, the compou d i l d from the grou (2-(3-(1-acetylpiperidin-4-yl)-1'-methyl- 1H,1'H- ]-1-yl)acetyl)gly and (2-(3-(1 acetylpiperidin-4-yl)-1'- methyl- indazol]-1-yl)ac e (82). In one e he compound is (2-(3- din-4-yl) 1' eth biindazol]-1-yl glycine (81). In one , the co nd ( ( ( ylpiperidin-4-y 1H,1'H-[4,6'- biindazol]-1-yl)acetyl)glycylglycine (82).

[0008] In certain embodiments, provided herein is a compound having the following formula wherein is ; and R3ais a five- to fifteen-membered spiro bic cycloalkyl compris nitrogen, wherein the at least one nitrogen is unsub substituted with kyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocy halo , arylalkyl, or heteroaryl; –C(O)-(three- to -eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted wit eroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, a ylalkyl, or heteroaryl); three- to -eight-membered heterocycloalkyl comprising ne nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl; -alkylene-(three- to eight- membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsub or substituted with alkyl, heteroalkyl alkenyl, alkynyl, acyl, cycloalkyl, heter l, haloalkyl, aryl, arylalkyl, or r an -alkylene-N(R3aa)C(O)alkyl wher hydrogen or alkyl; R3bis hydrog uoro. In certain embodiments, R3is , , , , or In certain embodiments, R4, when present, is hydro In certain embod drogen or methyl. In certain embodiments, R1is . In certain embodiments, the compound is selected from the group consisting of (2-(1'-(2-acetyl-2-azaspiro[3.3]heptan-6-yl)-5'-fluoro-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (83), (2-(1'-(1-acetylpiperidine-4-carbonyl)-5'-fluoro-1H,1'H-[4,6'- biindazol]-1-yl)acetyl)glycylglycine (84), (2-(1'-(1-acetylpiperidin-4-yl)-5'-fluoro-1H,1'H-[4,6'- biindazol]-1-yl)acetyl)glycylglycine (85), (2-(5'-fluoro-3-methyl-1'-((1-methylpiperidin-4- yl)methyl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (86), and (2-(1'-(2-acetamidoethyl)- 5'-fluoro-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (87). In one embodiment, the compound is (2-(1'-(2-acetyl-2-azaspiro[3.3]heptan-6-yl)-5'-fluoro-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (83). In one embodiment, the compound is (2-(1'-(1-acetylpiperidine-4- carbonyl)-5'-fluoro-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (84). In one embodiment, the compound is (2-(1'-(1-acetylpiperidin-4-yl)-5'-fluoro-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (85). In one embodiment, the compound is (2-(5'-fluoro-3-methyl-1'-((1- methylpiperidin-4-yl)methyl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (86). In one embodiment, the compound is (2-(1'-(2-acetamidoethyl)-5'-fluoro-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (87). In certain embodiments, provided herein is a compound having the following formula wherein is ; and R3, when present, is hydrogen; and R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl. In certain embodiments, R4, when present, is hydrogen or alkyl. In certain embodiments, R4is or . In certain embodiments, R1is . In certain embodiments, the compound is selected from the group consisting of (2-(3-(1-acetylazetidin-3-yl)-1H-indazol-1-yl)acetyl)glycylglycine (88) and (2-(3-(1-acetylpiperidin-4-yl)-1H-indazol-1-yl)acetyl)glycylglycine (89). In one embodiment, the compound is (2-(3-(1-acetylazetidin-3-yl)-1H-indazol-1-yl)acetyl)glycylglycine (88). In one embodiment, the compound is (2-(3-(1-acetylpiperidin-4-yl)-1H-indazol-1- yl)acetyl)glycylglycine (89). In certain embodiments, provided herein is a compound having the following formula wherein is ; and R3, when present, is hydrogen; R4, when rogen; and R1is In certain embodiments, the compound is selecte oup cons g o 1-yl)acetyl)glycylglycine (90) and methyl (2-(1H indol 1 yl)acetyl)glycygycinate (91). In one embodiment, the compound is (2-(1H- indazol-1-yl)acetyl)glycylglycine (90). In one embodiment, the compound is methyl (2-(1H-indol- 1-yl)acetyl)glycylglycinate (91). In certain embodiments, provided herein is a compou owing formula wh ; and R3, when present, is aryl or heteroaryl, wherein aryl o unsubstituted or substituted with alkyl, heteroalkyl, heterocycloalkyl, and / or when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl or –C(O)-heteroalkylene-NR4aR4bwherein R4aand R4bare independently hydrogen, alkyl, or acyl. In certain embodiments, R3is selected from the group consisting of , , , , , , , , and . In one embodiment, R3is . In one embodiment, R3is . In one embodiment, R3is . In one embodiment, R3is . In one embodiment, R3is . In one embodim . In one e . In one embodiment, R3is . In one embodiment, R3is . In one embodiment, R3is . In one embodiment, R3is . In one embodiment, R3is . In certain embodiments, R4is . In certain embodiments, R1is . In certain embodiments, the compound is selected from the group consisting of (2-(3-(1-acetylpiperidin-4-yl)-4-(naphthalen-2-yl)-1H- (92), (2-(3-(1-acetylpiperidin-4-yl)-4-(2-fluoro-4- glycylglycine (93), (2-(3-(1-acetylpiperidin-4-yl)-4-(2,6- 1-yl)acetyl)glycylglycine (94), (2-(3-(1-acetylpiperidin-4- cetyl)glycylglycine (95), (2-(3-(1-acetylpiperidin-4-yl)-4- (quinolin-7-yl)-1H-indazol-1-yl)acetyl)glycylglycine (96) (2 (3 (1-acetylpiperidin-4-yl)-4- (isoquinolin-6-yl)-1H-indazol-1-yl)acetyl)glycylglycine (97 acetylpiperidin-4-yl)-4-(3- methylbenzo[d]isoxazol-6-yl)-1H-indazol-1-yl)acetyl)glycy (98), (2-(3-(1- acetylpiperidin-4-yl)-4-(benzofuran-2-yl)-1H-indazol-1-yl)a lglycine (99), (2-(3-(1- acetylpiperidin-4-yl)-4-(benzofuran-6-yl) 1H indazol-1-yl)acetyl)glycylglycine (100), (2-(3-(1- ac din-4-yl)-4-(benzo[d]isothiaz 1H-indazol-1-yl)acetyl)glycy e (101), (2- (3 piperidin-4-yl)-4-(isoquinoli H-indazol-1-yl)acetyl)glycyl (102), and (2 etylpiperidin-4-yl)-4-(quinoli H-indazol-1-yl)acetyl)glycyl (103). In one embodiment, the compound is (2-(3-(1-acetylpiperidi 4 l) 4 (naphthalen-2-yl)-1H-indazol- 1-yl)acetyl)glycylglycine (92). In one embodiment, the c d is (2-(3-(1-acetylpiperidin-4- yl)-4-(2-fluoro-4-methylphenyl)-1H-indazol-1-yl)acetyl)g ine (93). In one embodiment, the compound is (2-(3-(1-acetylpiperidin-4-yl)-4-(2,6-d -methylphenyl)-1H-indazol-1- yl)acetyl)glycylglycine (94). In one embodiment, the compound is (2-(3-(1-acetylpiperidin-4-yl)- n-3-yl)-1H-indazol-1-yl)ace lglycine (95). In one embo compound 1-acetylpiperidin-4-yl)-4-(qu yl)-1H-indazol-1-yl)acetyl) ne (96). In diment, the compound is (2-( ylpiperidin-4-yl)-4-(isoquin H-indazol- 1-yl)acetyl)glycylglycine (97). In one embodiment, the compound is (2-(3 (1 acetylpiperidin-4- yl)-4-(3-methylb oxazol-6-yl)-1H-indazol-1-yl)acetyl)glycylglycine (98). In one embodiment, the nd is (2-(3-(1-acetylpiperidin-4-yl)-4-(benzofuran-2-yl)-1H-indazol-1- yl)acetyl)glycylg 9). In one embodiment, the compound is (2-(3-(1-acetylpiperidin-4-yl)- 4-(benzofuran-6-yl) 1H indazol-1-yl)acetyl)glycylglycine (100). In one embodiment, the compound is (2-(3-(1-acetylpiperidin-4-yl)-4-(benzo[d]isothiazol-6-yl)-1H-indazol-1- yl)acetyl)glycylglycine (101). In one embodiment, the compound is (2-(3-(1-acetylpiperidin-4-yl)- inolin-7-yl)-1H-indazol-1-yl) ine (102). In one embodiment, the nd is (2 ridin-4-yl)-4-(quinolin-6-yl)-1H-indazol-1- l)glycylglycine (103). In certain embodimen ein is a compound having the following formula wherein is ; and R3is . In certain embodiments, R4is . In certain embodiments, R1is . In one embodiment, the compound is methyl (2-(3-(1-(3-(2-(2-(2- aminoethoxy)ethoxy)ethoxy)propanoyl)piperidin-4-yl)-4-(5-methyl-6-morpholinopyridin-3-yl)- 1H-indazol-1-yl)acetyl)glycylglycinate (104). In certain embodiments, provided herein is a compound having the following formula wherein is ; R3, when present, is ; and R4, when present, is hydrogen. In certain embodiments, R3ais alkyl; R3bis hydrogen; and R3cis halo. In certain embodiments, R3is . In certain embodiments, R1is . In one embodiment, the compound is (2-(4-(5-fluoro-1-methyl-1H-indazol-6-yl)-1H-indol-1- yl)acetyl)glycylglycine (105). In certain embodiments, provided herein is a compound having the following formula where and present, is . In ce rogen and X4is nitrogen. In certain embodiments, R3ais alk is halo. In certain embodiments, R3is . In certain . In one embodiment, the compound is (2-(4-(5-fluoro-1-m y y zo[d]imidazol-1-yl)acetyl)glycylglycine n certain embodiments, provided herein is a compound having the following formula wherein is , X3is carbon, and X4is oxygen. In certain embodiments, R3ais alkyl; R3bis hydrogen; and R3cis halo. In certain embodiments, R3is . In certain emb . In one embodiment, the compound is (2-(7 methyl-1 n-3-yl)acetyl)glycylglycine (107). rtain em in is a compound having the following formula wherein is or and ent, is . In certain embodiments, R3ais alkyl; R3bis hydrogen; and R3cis halo. In certain R3is . ments, R1is . In one embodi ound is selected from ng of (2-(5-(5-fluoro-1-methyl-1H- indazol- -1-yl)ace ycylg -(5-fluoro-1-methyl-1H-indazol-6- yl)quinolin-4-yl)acetyl)glycylglycine (219), and (2-(4-(5-fluoro-1-methyl-1H-indazol-6- yl)quinolin-8-yl)acetyl)glycylglycine (109). In one embodiment, the compound is (2-(5-(5-fluoro- 1-methyl-1H-indazol-6-yl)naphthalen-1-yl)acetyl)glycylglycine (108). In one embodiment, the compound is (2-(8-(5-fluoro-1-methyl-1H-indazol-6-yl)quinolin-4-yl)acetyl)glycylglycine (219). In one embodiment, the compound is (2-(4-(5-fluoro-1-methyl-1H-indazol-6-yl)quinolin-8- yl)acetyl)glycylglycine (109).

[0009] In certain embodiments, provided herein is a compound having the following formula wherein is ; R3, when present, is ; and R4, when present, is heterocycloalkyl wherein heterocycloalkyl is unsubstituted or substituted with alkyl, alkenyl, alkynyl, heteroalkyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl heteroaryl, or –C(O)NR4aR4bwherbare independently hydrogen or alkyl. bodiments, R3ais alkyl; R3bis h R3cis halo. In certain embodiments, R3is . In certain embodiments, R4, when present, is heterocycloalkyl wherein heterocycloalkyl is unsubstituted or substituted with –C(O)NR4aR4bwherein R4aand R4bare independently hydrogen or alkyl. In certain embodiments, R4is . In certain e s . In one embodiment, the compound is (2-(5'-fluoro-1'-methyl- 3 (4 (methylcarbamoyl)piperidin-1-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (110).

[0010] In certain embodiments, provided herein is a compound having the following formu wherein ; R3, when present, is ; and R t, is a three- to heterocycloalkyl comprising at least one nitrog e at leas ne n bstituted or substituted with acyl, –C(O)- heteroalkylene-NR4aR4b, alkyl, –C(O)-alkylene-COOR5, –C(O)-alkylene-C(O)NR4aR4b, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl, wherein R4aand R4bare independently hydrogen, alkyl, or acyl. In certain embodiments, R3ais alkyl; R3bis hydrogen; and R3cis halo. In certain embodiments, R3is . In certain embodiments, R4, when present, is a three- to eight- membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl. In certain embodiments, R . In certain embodiments, R1i In one embodiment, the compounds is selected from the group consisting of piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)ethyl)glycylglycine (111), (2-(2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)acetamido)ethyl)glycine (112), and (5-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'- methyl-1H,1'H-[4,6'-biindazol]-1-yl)pentanoyl)glycine (113). In one embodiment, the compound is (2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)ethyl)glycylglycine (111). In one embodiment, the compound is (2-(2-(3-(1-acetylpiperidin-4- yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-bi etamido)ethyl)glycine (112). In one embodiment, the compound is (5-(3 din-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)pentanoyl)glycine (113 In certain embodimen ein is a compound having the following formula wherein is ; R3, when present, is heteroaryl wherein heteroaryl is unsubstituted or substituted with alkyl, heteroalkyl, heterocycloalkyl, and / or halo; R4, when present, is hydrogen; and R1is . In one embodiment, the compounds is (2-(4- (4-fluoro-1-methyl- -yl)-1H-indazol-1-yl)acetyl)glycylglycine (114) or (2-(4-(1- methyl-1H-pyrazol- zol-1-yl)acetyl)glycylglycine (115). In one embodiment, the compounds is (2- -methyl-1H-pyrazol-5-yl)-1H-indazol-1-yl)acetyl)glycylglycine (114). In one emb compound is (2-(4-(1-methyl-1H-pyrazol-5-yl)-1H-indazol-1- yl)acetyl)glycylglycine (115). In certain embodiments, provided herein is a compoun he following formula is ; R3, when present, is ; and R4, when p n. In certain embodiments, R3ais alkyl; R3bis hydrogen; and

[0011] R3cis halo. In certain embodiments, R3is . In certain embodiments, R1is . In one embodiment, the compounds is selected from the group consisting of (2- (5'-fluoro-7-hydroxy-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (116), (2-(5'- fluoro-1'-methyl-7-(trifluoromethoxy)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (117), (2-(5'-fluoro-1',7-dimethyl-1H,1'H-[4 l)acetyl)glycylglycine (118), (2-(5'-fluoro- 7-meth -1H,1'H-[4,6'-bi tyl)glycylglycine (119), (2-(5'-fluoro-1',6- dimeth 6'-biindazol]-1-y ycine (120), and (2-(5'-fluoro-1',5- dimeth 6'-biindaz 1-y ycine (121). In one embodiment, the compo uoro-7-hy xy-1 methyl 1H,1H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (116). In one embodiment, the compound is (2-(5'-fluoro-1'-methyl-7-(trifluoromethoxy)-1H,1'H- [4,6'-biindazol]-1-yl)acetyl)glycylg n one embodiment, the compound is (2-(5'- fluoro-1',7-dimethyl-1H,1'H-[4,6'-b acetyl)glycylglycine (118). In one embodiment, the compound is -methoxy-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (119). In one embodiment, the compound is (2-(5'-fluoro-1',6-dimethyl- 1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (120). In one embodiment, the compound is (2- (5'-fluoro-1',5-dimethyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (121). In certain embodiments, provided is a compound having the following formula or a pharma able salt thereof, w s hydrogen or C1-5alkyl; R5is hydrogen or C1-5alkyl; R9is ; each R9ais hydrogen or alkyl; R9bis -C(O)OR9cor ; each R9cis C1-5alkyl; bb is one or two; and R3cis hydrogen, halogen, or CN. In certain each R9ais hydrogen. In certain embodiments, R9cis hydrogen or methyl. In certain embodiments, bb is one. In certain embodiments, bb is two. In certain embodiments, provided is a compound having the following formula or a pharmaceutically acceptable salt thereof as described elsewhere herein, wherein R3ais –C(O)-alkylene-C(O)R3aaawherein R3aaais –OR7a, –NR7aR7bor alkyl; R3bis hydrogen; and R3cis fluoro. In certain embodiments, provided is a compound having the following formula . In certain embodiments, R3is , , or . In certain embodiments, R4, when present, is hydrogen or alkyl. In certain embodiments, R4is hydrogen, methyl, or isopropyl. In certain embodiments, R1is . In certain embodiments, the compound is selected from the group consisting of 4-(1-(2-((2-((carboxymethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)- 5'-fluoro-3-methyl-1H,1'H-[4,6'-biindazol]-1'-yl)-4-oxobutanoic acid (122), 4-(5'-fluoro-1-(2-((2- ((2-methoxy-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-3-methyl-1H,1'H-[4,6'- biindazol]-1'-yl)-4-oxobutanoic acid (123), 4-(1-(2-((2-((2-(tert-butoxy)-2-oxoethyl)amino)-2- oxoethyl)amino)-2-oxoethyl)-5'-fluoro-3-methyl-1H,1'H-[4,6'-biindazol]-1'-yl)-4-oxobutanoic acid (124), (2-(1'-(4-amino-4-oxobutanoyl)-5'-fluoro-3-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (125), methyl (2-(1'-(4-amino-4-oxobutanoyl)-5'-fluoro-3-methyl-1H,1'H- [4,6'-biindazol]-1-yl)acetyl)glycylglycinate (126), tert-butyl (2-(1'-(4-amino-4-oxobutanoyl)-5'- fluoro-3-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (127), (2-(5'-fluoro-3- methyl-1'-(4-oxopentanoyl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (128), methyl (2- (5'-fluoro-3-methyl-1'-(4-oxopentanoyl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (129), tert-butyl (2-(5'-fluoro-3-methyl-1'-(4-oxopentanoyl)-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (130), 4-(1-(2-((2-((carboxymethyl)amino)-2-oxoethyl)amino)-2- oxoethyl)-5'-fluoro-3-isopropyl-1H,1'H-[4,6'-biindazol]-1'-yl)-4-oxobutanoic acid (131), 4-(5'- fluoro-3-isopropyl-1-(2-((2-((2-methoxy-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)- 1H,1'H-[4,6'-biindazol]-1'-yl)-4-oxobutanoic acid (132), 4-(1-(2-((2-((2-(tert-butoxy)-2- oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-5'-fluoro-3-isopropyl-1H,1'H-[4,6'-biindazol]- 1'-yl)-4-oxobutanoic acid (133), (2-(1'-(4-amino-4-oxobutanoyl)-5'-fluoro-3-isopropyl-1H,1'H- [4,6'-biindazol]-1-yl)acetyl)glycylglycine (134), methyl (2-(1'-(4-amino-4-oxobutanoyl)-5'- fluoro-3-isopropyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (135), tert-butyl (2-(1'-(4- amino-4-oxobutanoyl)-5'-fluoro-3-isopropyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (136), (2-(5'-fluoro-3-isopropyl-1'-(4-oxopentanoyl)-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (137), methyl (2-(5'-fluoro-3-isopropyl-1'-(4-oxopentanoyl)-1H,1'H-[4,6'- biindazol]-1-yl)acetyl)glycylglycinate (138), and tert-butyl (2-(5'-fluoro-3-isopropyl-1'-(4- oxopentanoyl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (139). In one embodiment, the compounds is 4-(1-(2-((2-((carboxymethyl)amino)-2- oxoethyl)amino)-2-oxoethyl)-5'-fluoro-3-methyl-1H,1'H-[4,6'-biindazol]-1'-yl)-4-oxobutanoic acid (122). In one embodiment, the compounds is 4-(5'-fluoro-1-(2-((2-((2-methoxy-2- oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-3-methyl-1H,1'H-[4,6'-biindazol]-1'-yl)-4- oxobutanoic acid (123). In one embodiment, the compounds is 4-(1-(2-((2-((2-(tert-butoxy)-2- oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-5'-fluoro-3-methyl-1H,1'H-[4,6'-biindazol]-1'- yl)-4-oxobutanoic acid (124). In one embodiment, the compounds is (2-(1'-(4-amino-4- oxobutanoyl)-5'-fluoro-3-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (125). In one embodiment, the compounds is methyl (2-(1'-(4-amino-4-oxobutanoyl)-5'-fluoro-3-methyl- 1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (126). In one embodiment, the compounds is tert-butyl (2-(1'-(4-amino-4-oxobutanoyl)-5'-fluoro-3-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (127). In one embodiment, the compounds is (2-(5'-fluoro-3-methyl-1'- (4-oxopentanoyl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (128). In one embodiment, the compounds is methyl (2-(5'-fluoro-3-methyl-1'-(4-oxopentanoyl)-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (129). In one embodiment, the compounds is tert-butyl (2-(5'-fluoro-3- methyl-1'-(4-oxopentanoyl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (130). In one embodiment, the compounds is 4-(1-(2-((2-((carboxymethyl)amino)-2-oxoethyl)amino)-2- oxoethyl)-5'-fluoro-3-isopropyl-1H,1'H-[4,6'-biindazol]-1'-yl)-4-oxobutanoic acid (131). In one embodiment, the compounds is 4-(5'-fluoro-3-isopropyl-1-(2-((2-((2-methoxy-2- oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-1H,1'H-[4,6'-biindazol]-1'-yl)-4-oxobutanoic acid (132). In one embodiment, the compounds is 4-(1-(2-((2-((2-(tert-butoxy)-2- oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-5'-fluoro-3-isopropyl-1H,1'H-[4,6'-biindazol]- 1'-yl)-4-oxobutanoic acid (133). In one embodiment, the compounds is (2-(1'-(4-amino-4- oxobutanoyl)-5'-fluoro-3-isopropyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (134). In one embodiment, the compounds is methyl (2-(1'-(4-amino-4-oxobutanoyl)-5'-fluoro-3-isopropyl- 1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (135). In one embodiment, the compounds is tert-butyl (2-(1'-(4-amino-4-oxobutanoyl)-5'-fluoro-3-isopropyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (136). In one embodiment, the compounds is (2-(5'-fluoro-3-isopropyl- 1'-(4-oxopentanoyl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (137). In one embodiment, the compounds is methyl (2-(5'-fluoro-3-isopropyl-1'-(4-oxopentanoyl)-1H,1'H-[4,6'-biindazol]- 1-yl)acetyl)glycylglycinate (138). In one embodiment, the compounds is tert-butyl (2-(5'-fluoro- 3-isopropyl-1'-(4-oxopentanoyl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (139). In certain embodiments, provided is a compound having the following formula or a pharmaceutically acceptable salt thereof as described elsewhere herein, wherein R3is , , , or . In certain embodiments, R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is substituted with –C(O)-alkylene-C(O)R3aaawherein R3aaais –OR7a, –NR7aR7bor alkyl; or alkyl. In certain embodiments, provided is a compound having the following formula wherein R4aais –C(O)-alkylene-C(O)R3aaawherein R3aaais –OR7a, –NR7aR7bor alkyl; or alkyl. In certain embodiments, R4aais methyl, , , or . In certain embodiments, the compound is selected from the group consisting of 2-(4-((2-(5'-fluoro-1'-methyl-3-(1-methylpiperidin-4-yl)-1H,1'H- [4,6'-biindazol]-1-yl)acetamido)methyl)-1H-1,2,3-triazol-1-yl)acetic acid (140), methyl 2-(4-((2- (5'-fluoro-1'-methyl-3-(1-methylpiperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)methyl)- 1H-1,2,3-triazol-1-yl)acetate (141), tert-butyl 2-(4-((2-(5'-fluoro-1'-methyl-3-(1-methylpiperidin- 4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)methyl)-1H-1,2,3-triazol-1-yl)acetate (142), 4-(4- (1-(2-(((1-(carboxymethyl)-1H-1,2,3-triazol-4-yl)methyl)amino)-2-oxoethyl)-5'-fluoro-1'- methyl-1H,1'H-[4,6'-biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid (143), 4-(4-(5'-fluoro-1- (2-(((1-(2-methoxy-2-oxoethyl)-1H-1,2,3-triazol-4-yl)methyl)amino)-2-oxoethyl)-1'-methyl- 1H,1'H-[4,6'-biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid (144), 4-(4-(1-(2-(((1-(2-(tert- butoxy)-2-oxoethyl)-1H-1,2,3-triazol-4-yl)methyl)amino)-2-oxoethyl)-5'-fluoro-1'-methyl- 1H,1'H-[4,6'-biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid (145), 2-(4-((2-(3-(1-(4-amino-4- oxobutanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)methyl)- 1H-1,2,3-triazol-1-yl)acetic acid (146), methyl 2-(4-((2-(3-(1-(4-amino-4-oxobutanoyl)piperidin- 4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)methyl)-1H-1,2,3-triazol-1- yl)acetate (147), tert-butyl 2-(4-((2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-5'-fluoro-1'- methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)methyl)-1H-1,2,3-triazol-1-yl)acetate (148), 2-(4- ((2-(5'-fluoro-1'-methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1- yl)acetamido)methyl)-1H-1,2,3-triazol-1-yl)acetic acid (149), methyl 2-(4-((2-(5'-fluoro-1'- methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)methyl)- 1H-1,2,3-triazol-1-yl)acetate (150), and tert-butyl 2-(4-((2-(5'-fluoro-1'-methyl-3-(1-(4- oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)methyl)-1H-1,2,3-triazol- 1-yl)acetate (151). In one embodiment, the compound is 2-(4-((2-(5'-fluoro-1'-methyl-3-(1- methylpiperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)methyl)-1H-1,2,3-triazol-1- yl)acetic acid (140). In one embodiment, the compound is methyl 2-(4-((2-(5'-fluoro-1'-methyl-3- (1-methylpiperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)methyl)-1H-1,2,3-triazol-1- yl)acetate (141). In one embodiment, the compound is tert-butyl 2-(4-((2-(5'-fluoro-1'-methyl-3- (1-methylpiperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)methyl)-1H-1,2,3-triazol-1- yl)acetate (142). In one embodiment, the compound is 4-(4-(1-(2-(((1-(carboxymethyl)-1H-1,2,3- triazol-4-yl)methyl)amino)-2-oxoethyl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-3- yl)piperidin-1-yl)-4-oxobutanoic acid (143). In one embodiment, the compound is 4-(4-(5'-fluoro- 1-(2-(((1-(2-methoxy-2-oxoethyl)-1H-1,2,3-triazol-4-yl)methyl)amino)-2-oxoethyl)-1'-methyl- 1H,1'H-[4,6'-biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid (144). In one embodiment, the compound is 4-(4-(1-(2-(((1-(2-(tert-butoxy)-2-oxoethyl)-1H-1,2,3-triazol-4-yl)methyl)amino)-2- oxoethyl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid (145). In one embodiment, the compound is 2-(4-((2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4- yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)methyl)-1H-1,2,3-triazol-1- yl)acetic acid (146). In one embodiment, the compound is methyl 2-(4-((2-(3-(1-(4-amino-4- oxobutanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)methyl)- 1H-1,2,3-triazol-1-yl)acetate (147). In one embodiment, the compound is tert-butyl 2-(4-((2-(3- (1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetamido)methyl)-1H-1,2,3-triazol-1-yl)acetate (148). In one embodiment, the compound is 2- (4-((2-(5'-fluoro-1'-methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1- yl)acetamido)methyl)-1H-1,2,3-triazol-1-yl)acetic acid (149). In one embodiment, the compound is methyl 2-(4-((2-(5'-fluoro-1'-methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'- biindazol]-1-yl)acetamido)methyl)-1H-1,2,3-triazol-1-yl)acetate (150). In one embodiment, the compound is tert-butyl 2-(4-((2-(5'-fluoro-1'-methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)- 1H,1'H-[4,6'-biindazol]-1-yl)acetamido)methyl)-1H-1,2,3-triazol-1-yl)acetate (151). In certain embodiments, provided is a compound having the following formula or a pharmaceutically acceptable salt thereof as described elsewhere herein, wherein R4, when present, is a five- to fifteen-membered spiro bicyclic heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, or –C(O)-alkylene-C(O)R3aaawherein R3aaais –OR7a, –NR7aR7bor alkyl. In certain embodiments, provided is a compound having the following formula wherein R3bis alkyl and R3cis halo. In certain embodiments, the compound is selected from the group consisting of 4-(6-(1-(2-((2- ((carboxymethyl)amino)-2-oxoethyl)(methyl)amino)-2-oxoethyl)-5'-fluoro-1'-methyl-1H,1'H- [4,6'-biindazol]-3-yl)-2-azaspiro[3.3]heptan-2-yl)-4-oxobutanoic acid (152), 4-(6-(5'-fluoro-1-(2- ((2-((2-methoxy-2-oxoethyl)amino)-2-oxoethyl)(methyl)amino)-2-oxoethyl)-1'-methyl-1H,1'H- [4,6'-biindazol]-3-yl)-2-azaspiro[3.3]heptan-2-yl)-4-oxobutanoic acid (153), 4-(6-(1-(2-((2-((2- (tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)(methyl)amino)-2-oxoethyl)-5'-fluoro-1'-methyl- 1H,1'H-[4,6'-biindazol]-3-yl)-2-azaspiro[3.3]heptan-2-yl)-4-oxobutanoic acid (154), N-(2-(3-(2- (4-amino-4-oxobutanoyl)-2-azaspiro[3.3]heptan-6-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)acetyl)-N-methylglycylglycine (155), methyl N-(2-(3-(2-(4-amino-4- oxobutanoyl)-2-azaspiro[3.3]heptan-6-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)-N-methylglycylglycinate (156), tert-butyl N-(2-(3-(2-(4-amino-4-oxobutanoyl)-2- azaspiro[3.3]heptan-6-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N- methylglycylglycinate (157), N-(2-(5'-fluoro-1'-methyl-3-(2-(4-oxopentanoyl)-2- azaspiro[3.3]heptan-6-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N-methylglycylglycine (158), methyl N-(2-(5'-fluoro-1'-methyl-3-(2-(4-oxopentanoyl)-2-azaspiro[3.3]heptan-6-yl)-1H,1'H- [4,6'-biindazol]-1-yl)acetyl)-N-methylglycylglycinate (159), and tert-butyl N-(2-(5'-fluoro-1'- methyl-3-(2-(4-oxopentanoyl)-2-azaspiro[3.3]heptan-6-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)- N-methylglycylglycinate (160). In one embodiment, the compounds is 4-(6-(1-(2-((2-((carboxymethyl)amino)-2- oxoethyl)(methyl)amino)-2-oxoethyl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-3-yl)-2- azaspiro[3.3]heptan-2-yl)-4-oxobutanoic acid (152). In one embodiment, the compounds is 4-(6- (5'-fluoro-1-(2-((2-((2-methoxy-2-oxoethyl)amino)-2-oxoethyl)(methyl)amino)-2-oxoethyl)-1'- methyl-1H,1'H-[4,6'-biindazol]-3-yl)-2-azaspiro[3.3]heptan-2-yl)-4-oxobutanoic acid (153). In one embodiment, the compounds is 4-(6-(1-(2-((2-((2-(tert-butoxy)-2-oxoethyl)amino)-2- oxoethyl)(methyl)amino)-2-oxoethyl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-3-yl)-2- azaspiro[3.3]heptan-2-yl)-4-oxobutanoic acid (154). In one embodiment, the compounds is N-(2- (3-(2-(4-amino-4-oxobutanoyl)-2-azaspiro[3.3]heptan-6-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)acetyl)-N-methylglycylglycine (155). In one embodiment, the compounds is methyl N-(2-(3-(2-(4-amino-4-oxobutanoyl)-2-azaspiro[3.3]heptan-6-yl)-5'-fluoro-1'-methyl- 1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N-methylglycylglycinate (156). In one embodiment, the compounds is tert-butyl N-(2-(3-(2-(4-amino-4-oxobutanoyl)-2-azaspiro[3.3]heptan-6-yl)-5'- fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N-methylglycylglycinate (157). In one embodiment, the compounds is N-(2-(5'-fluoro-1'-methyl-3-(2-(4-oxopentanoyl)-2- azaspiro[3.3]heptan-6-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N-methylglycylglycine (158). In one embodiment, the compounds is methyl N-(2-(5'-fluoro-1'-methyl-3-(2-(4-oxopentanoyl)-2- azaspiro[3.3]heptan-6-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N-methylglycylglycinate (159). In one embodiment, the compounds is tert-butyl N-(2-(5'-fluoro-1'-methyl-3-(2-(4-oxopentanoyl)-2- azaspiro[3.3]heptan-6-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N-methylglycylglycinate (160). In certain embodiments, provided is a compound having the following formula or a pharmaceutically acceptable salt thereof as described elsewhere herein, wherein R3is , , , , or . In certain embodiments, R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with –C(O)- alkylene-C(O)R3aaawherein R3aaais –OR7a, –NR7aR7bor alkyl. In certain embodiments, R1is . In certain embodiments, the formula of the compound is selected from the group consisting of ,

[0012] , , , and . In one embodiment, the formula of the compound is . In one embodiment, the formula of the compound is . In one embodiment, the formula of the compound is

[0013] . In one embodiment, the formula of the compound is . In one embodiment, the formula of the compound is . In certain embodiments, the compound is selected from the group consisting of 4-(4-(1-(2-((2-((carboxymethyl)amino)-2- oxoethyl)amino)-2-oxoethyl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-3-yl)piperidin-1-yl)-4- oxobutanoic acid (161), 4-(4-(5'-fluoro-1-(2-((2-((2-methoxy-2-oxoethyl)amino)-2- oxoethyl)amino)-2-oxoethyl)-1'-methyl-1H,1'H-[4,6'-biindazol]-3-yl)piperidin-1-yl)-4- oxobutanoic acid (162), 4-(4-(1-(2-((2-((2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)amino)-2- oxoethyl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid (163), (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)acetyl)glycylglycine (164), methyl (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4- yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (165), tert-butyl (2-(3- (1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (166), (2-(5'-fluoro-1'-methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)- 1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (167), methyl (2-(5'-fluoro-1'-methyl-3-(1-(4- oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (168), tert- butyl (2-(5'-fluoro-1'-methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (169), 4-(4-(1-(2-((2-((carboxymethyl)amino)-2- oxoethyl)(methyl)amino)-2-oxoethyl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-3-yl)piperidin- 1-yl)-4-oxobutanoic acid (170), 4-(4-(5'-fluoro-1-(2-((2-((2-methoxy-2-oxoethyl)amino)-2- oxoethyl)(methyl)amino)-2-oxoethyl)-1'-methyl-1H,1'H-[4,6'-biindazol]-3-yl)piperidin-1-yl)-4- oxobutanoic acid (171), 4-(4-(1-(2-((2-((2-(tert-butoxy)-2-oxoethyl)amino)-2- oxoethyl)(methyl)amino)-2-oxoethyl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-3-yl)piperidin- 1-yl)-4-oxobutanoic acid (172), N-(2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-5'-fluoro-1'- methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N-methylglycylglycine (173), methyl N-(2-(3-(1-(4- amino-4-oxobutanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N- methylglycylglycinate (174), tert-butyl N-(2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-5'- fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N-methylglycylglycinate (175), N-(2-(5'- fluoro-1'-methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N- methylglycylglycine (176), methyl N-(2-(5'-fluoro-1'-methyl-3-(1-(4-oxopentanoyl)piperidin-4- yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N-methylglycylglycinate (177), tert-butyl N-(2-(5'- fluoro-1'-methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N- methylglycylglycinate (178), 4-(4-(1-(2-((2-((carboxymethyl)amino)-2-oxoethyl)amino)-2- oxoethyl)-1'-methyl-1H,1'H-[4,6'-biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid (179), 4-(4- (1-(2-((2-((2-methoxy-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-1'-methyl-1H,1'H- [4,6'-biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid (180), 4-(4-(1-(2-((2-((2-(tert-butoxy)-2- oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-1'-methyl-1H,1'H-[4,6'-biindazol]-3- yl)piperidin-1-yl)-4-oxobutanoic acid (181), (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-1'- methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (182), methyl (2-(3-(1-(4-amino-4- oxobutanoyl)piperidin-4-yl)-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (183), tert-butyl (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (184), (2-(1'-methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'- biindazol]-1-yl)acetyl)glycylglycine (185), methyl (2-(1'-methyl-3-(1-(4-oxopentanoyl)piperidin- 4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (186), tert-butyl (2-(1'-methyl-3-(1-(4- oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (187), 4-(4-(1- (2-((2-((carboxymethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-4-(5-fluoro-1-methyl-1H- indazol-6-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)piperidin-1-yl)-4-oxobutanoic acid (188), 4-(4-(4- (5-fluoro-1-methyl-1H-indazol-6-yl)-1-(2-((2-((2-methoxy-2-oxoethyl)amino)-2- oxoethyl)amino)-2-oxoethyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)piperidin-1-yl)-4-oxobutanoic acid (189), 4-(4-(1-(2-((2-((2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-4-(5- fluoro-1-methyl-1H-indazol-6-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)piperidin-1-yl)-4-oxobutanoic acid (190), (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-4-(5-fluoro-1-methyl-1H-indazol-6- yl)-1H-pyrazolo[3,4-b]pyridin-1-yl)acetyl)glycylglycine (191), methyl (2-(3-(1-(4-amino-4- oxobutanoyl)piperidin-4-yl)-4-(5-fluoro-1-methyl-1H-indazol-6-yl)-1H-pyrazolo[3,4-b]pyridin- 1-yl)acetyl)glycylglycinate (192), tert-butyl (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-4- (5-fluoro-1-methyl-1H-indazol-6-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl)acetyl)glycylglycinate (193), (2-(4-(5-fluoro-1-methyl-1H-indazol-6-yl)-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H- pyrazolo[3,4-b]pyridin-1-yl)acetyl)glycylglycine (194), methyl (2-(4-(5-fluoro-1-methyl-1H- indazol-6-yl)-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H-pyrazolo[3,4-b]pyridin-1- yl)acetyl)glycylglycinate (195), tert-butyl (2-(4-(5-fluoro-1-methyl-1H-indazol-6-yl)-3-(1-(4- oxopentanoyl)piperidin-4-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl)acetyl)glycylglycinate (196), 4-(4- (1-(2-((2-((carboxymethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-7'-fluoro-1'-methyl-1H,1'H- [4,6'-biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid (197), 4-(4-(7'-fluoro-1-(2-((2-((2- methoxy-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-1'-methyl-1H,1'H-[4,6'-biindazol]- 3-yl)piperidin-1-yl)-4-oxobutanoic acid (198), 4-(4-(1-(2-((2-((2-(tert-butoxy)-2- oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-7'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-3- yl)piperidin-1-yl)-4-oxobutanoic acid (199), (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-7'- fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (200), methyl (2-(3-(1-(4- amino-4-oxobutanoyl)piperidin-4-yl)-7'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (201), tert-butyl (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-7'- fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (202), (2-(7'-fluoro-1'- methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (203), methyl (2-(7'-fluoro-1'-methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'- biindazol]-1-yl)acetyl)glycylglycinate (204), and tert-butyl (2-(7'-fluoro-1'-methyl-3-(1-(4- oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (205). In one embodiment, the compound is 4-(4-(1-(2-((2-((carboxymethyl)amino)-2- oxoethyl)amino)-2-oxoethyl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-3-yl)piperidin-1-yl)-4- oxobutanoic acid (161). In one embodiment, the compound is 4-(4-(5'-fluoro-1-(2-((2-((2- methoxy-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-1'-methyl-1H,1'H-[4,6'-biindazol]- 3-yl)piperidin-1-yl)-4-oxobutanoic acid (162). In one embodiment, the compound is 4-(4-(1-(2- ((2-((2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-5'-fluoro-1'-methyl- 1H,1'H-[4,6'-biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid (163). In one embodiment, the compound is (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)acetyl)glycylglycine (164). In one embodiment, the compound is methyl (2-(3-(1- (4-amino-4-oxobutanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (165). In one embodiment, the compound is tert-butyl (2-(3-(1-(4- amino-4-oxobutanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (166). In one embodiment, the compound is (2-(5'-fluoro-1'-methyl-3- (1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (167). In one embodiment, the compound is methyl (2-(5'-fluoro-1'-methyl-3-(1-(4- oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (168). In one embodiment, the compound is tert-butyl (2-(5'-fluoro-1'-methyl-3-(1-(4-oxopentanoyl)piperidin- 4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (169). In one embodiment, the compound is 4-(4-(1-(2-((2-((carboxymethyl)amino)-2-oxoethyl)(methyl)amino)-2-oxoethyl)-5'- fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid (170). In one embodiment, the compound is 4-(4-(5'-fluoro-1-(2-((2-((2-methoxy-2-oxoethyl)amino)-2- oxoethyl)(methyl)amino)-2-oxoethyl)-1'-methyl-1H,1'H-[4,6'-biindazol]-3-yl)piperidin-1-yl)-4- oxobutanoic acid (171). In one embodiment, the compound is 4-(4-(1-(2-((2-((2-(tert-butoxy)-2- oxoethyl)amino)-2-oxoethyl)(methyl)amino)-2-oxoethyl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid (172). In one embodiment, the compound is N- (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)-N-methylglycylglycine (173). In one embodiment, the compound is methyl N-(2-(3-(1- (4-amino-4-oxobutanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)- N-methylglycylglycinate (174). In one embodiment, the compound is tert-butyl N-(2-(3-(1-(4- amino-4-oxobutanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N- methylglycylglycinate (175). In one embodiment, the compound is N-(2-(5'-fluoro-1'-methyl-3- (1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N-methylglycylglycine (176). In one embodiment, the compound is methyl N-(2-(5'-fluoro-1'-methyl-3-(1-(4- oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N-methylglycylglycinate (177). In one embodiment, the compound is tert-butyl N-(2-(5'-fluoro-1'-methyl-3-(1-(4- oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N-methylglycylglycinate (178). In one embodiment, the compound is 4-(4-(1-(2-((2-((carboxymethyl)amino)-2- oxoethyl)amino)-2-oxoethyl)-1'-methyl-1H,1'H-[4,6'-biindazol]-3-yl)piperidin-1-yl)-4- oxobutanoic acid (179). In one embodiment, the compound is 4-(4-(1-(2-((2-((2-methoxy-2- oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-1'-methyl-1H,1'H-[4,6'-biindazol]-3- yl)piperidin-1-yl)-4-oxobutanoic acid (180). In one embodiment, the compound is 4-(4-(1-(2-((2- ((2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-1'-methyl-1H,1'H-[4,6'- biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid (181). In one embodiment, the compound is (2- (3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (182). In one embodiment, the compound is methyl (2-(3-(1-(4-amino-4- oxobutanoyl)piperidin-4-yl)-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (183). In one embodiment, the compound is tert-butyl (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)- 1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (184). In one embodiment, the compound is (2-(1'-methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (185). In one embodiment, the compound is methyl (2-(1'-methyl-3-(1-(4- oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (186). In one embodiment, the compound is tert-butyl (2-(1'-methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)- 1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (187). In one embodiment, the compound is 4-(4-(1-(2-((2-((carboxymethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-4-(5-fluoro-1-methyl- 1H-indazol-6-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)piperidin-1-yl)-4-oxobutanoic acid (188). In one embodiment, the compound is 4-(4-(4-(5-fluoro-1-methyl-1H-indazol-6-yl)-1-(2-((2-((2- methoxy-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-1H-pyrazolo[3,4-b]pyridin-3- yl)piperidin-1-yl)-4-oxobutanoic acid (189). In one embodiment, the compound is 4-(4-(1-(2-((2- ((2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-4-(5-fluoro-1-methyl-1H- indazol-6-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)piperidin-1-yl)-4-oxobutanoic acid (190). In one embodiment, the compound is (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-4-(5-fluoro-1- methyl-1H-indazol-6-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl)acetyl)glycylglycine (191). In one embodiment, the compound is methyl (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-4-(5- fluoro-1-methyl-1H-indazol-6-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl)acetyl)glycylglycinate (192). In one embodiment, the compound is tert-butyl (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)- 4-(5-fluoro-1-methyl-1H-indazol-6-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl)acetyl)glycylglycinate (193). In one embodiment, the compound is (2-(4-(5-fluoro-1-methyl-1H-indazol-6-yl)-3-(1-(4- oxopentanoyl)piperidin-4-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl)acetyl)glycylglycine (194). In one embodiment, the compound is methyl (2-(4-(5-fluoro-1-methyl-1H-indazol-6-yl)-3-(1-(4- oxopentanoyl)piperidin-4-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl)acetyl)glycylglycinate (195). In one embodiment, the compound is tert-butyl (2-(4-(5-fluoro-1-methyl-1H-indazol-6-yl)-3-(1-(4- oxopentanoyl)piperidin-4-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl)acetyl)glycylglycinate (196). In one embodiment, the compound is 4-(4-(1-(2-((2-((carboxymethyl)amino)-2-oxoethyl)amino)-2- oxoethyl)-7'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid (197). In one embodiment, the compound is 4-(4-(7'-fluoro-1-(2-((2-((2-methoxy-2- oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-1'-methyl-1H,1'H-[4,6'-biindazol]-3- yl)piperidin-1-yl)-4-oxobutanoic acid (198). In one embodiment, the compound is 4-(4-(1-(2-((2- ((2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-7'-fluoro-1'-methyl-1H,1'H- [4,6'-biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid (199). In one embodiment, the compound is (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-7'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]- 1-yl)acetyl)glycylglycine (200). In one embodiment, the compound is methyl (2-(3-(1-(4-amino- 4-oxobutanoyl)piperidin-4-yl)-7'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (201). In one embodiment, the compound is tert-butyl (2-(3-(1-(4- amino-4-oxobutanoyl)piperidin-4-yl)-7'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (202). In one embodiment, the compound is (2-(7'-fluoro-1'-methyl-3- (1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (203). In one embodiment, the compound is methyl (2-(7'-fluoro-1'-methyl-3-(1-(4- oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (204). In one embodiment, the compound is tert-butyl (2-(7'-fluoro-1'-methyl-3-(1-(4-oxopentanoyl)piperidin- 4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (205).

[0014] In certain embodiments, provided is a compound having the following formula or a pharmaceutically acceptable salt thereof as described elsewhere herein, wherein R3ais –C(O)-(three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, or –C(O)-alkylene- C(O)R3aaawherein R3aaais –OR7a, –NR7aR7bor alkyl); R3bis hydrogen; and R3cis fluoro. In certain embodiments, R4, when present, is hydrogen or alkyl. In certain embodiments, R1is . In certain embodiments, provided is a compound having the following formula . In certain embodiments, the compound is selected from the group consisting of 4-(4-(1-(2-((2-((carboxymethyl)amino)-2- oxoethyl)amino)-2-oxoethyl)-5'-fluoro-1H,1'H-[4,6'-biindazole]-1'-carbonyl)piperidin-1-yl)-4- oxobutanoic acid (206), 4-(4-(5'-fluoro-1-(2-((2-((2-methoxy-2-oxoethyl)amino)-2- oxoethyl)amino)-2-oxoethyl)-1H,1'H-[4,6'-biindazole]-1'-carbonyl)piperidin-1-yl)-4-oxobutanoic acid (207), 4-(4-(1-(2-((2-((2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-5'- fluoro-1H,1'H-[4,6'-biindazole]-1'-carbonyl)piperidin-1-yl)-4-oxobutanoic acid (208), (2-(1'-(1- (4-amino-4-oxobutanoyl)piperidine-4-carbonyl)-5'-fluoro-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (209), methyl (2-(1'-(1-(4-amino-4-oxobutanoyl)piperidine-4-carbonyl)- 5'-fluoro-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (210), tert-butyl (2-(1'-(1-(4-amino- 4-oxobutanoyl)piperidine-4-carbonyl)-5'-fluoro-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (211), (2-(5'-fluoro-1'-(1-(4-oxopentanoyl)piperidine-4-carbonyl)- 1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (212), methyl (2-(5'-fluoro-1'-(1-(4- oxopentanoyl)piperidine-4-carbonyl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (213), and tert-butyl (2-(5'-fluoro-1'-(1-(4-oxopentanoyl)piperidine-4-carbonyl)-1H,1'H-[4,6'- biindazol]-1-yl)acetyl)glycylglycinate (214). In one embodiment, the compound is 4-(4-(1-(2-((2-((carboxymethyl)amino)-2- oxoethyl)amino)-2-oxoethyl)-5'-fluoro-1H,1'H-[4,6'-biindazole]-1'-carbonyl)piperidin-1-yl)-4- oxobutanoic acid (206). In one embodiment, the compound is 4-(4-(5'-fluoro-1-(2-((2-((2- methoxy-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-1H,1'H-[4,6'-biindazole]-1'- carbonyl)piperidin-1-yl)-4-oxobutanoic acid (207). In one embodiment, the compound is 4-(4-(1- (2-((2-((2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-5'-fluoro-1H,1'H- [4,6'-biindazole]-1'-carbonyl)piperidin-1-yl)-4-oxobutanoic acid (208). In one embodiment, the compound is (2-(1'-(1-(4-amino-4-oxobutanoyl)piperidine-4-carbonyl)-5'-fluoro-1H,1'H-[4,6'- biindazol]-1-yl)acetyl)glycylglycine (209). In one embodiment, the compound is methyl (2-(1'-(1- (4-amino-4-oxobutanoyl)piperidine-4-carbonyl)-5'-fluoro-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (210). In one embodiment, the compound is tert-butyl (2-(1'-(1-(4- amino-4-oxobutanoyl)piperidine-4-carbonyl)-5'-fluoro-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (211). In one embodiment, the compound is (2-(5'-fluoro-1'-(1-(4- oxopentanoyl)piperidine-4-carbonyl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (212). In one embodiment, the compound is methyl (2-(5'-fluoro-1'-(1-(4-oxopentanoyl)piperidine-4- carbonyl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (213). In one embodiment, the compound is tert-butyl (2-(5'-fluoro-1'-(1-(4-oxopentanoyl)piperidine-4-carbonyl)-1H,1'H-[4,6'- biindazol]-1-yl)acetyl)glycylglycinate (214). In certain embodiments, provided is a compound having the following formula or a pharmaceutically acceptable salt thereof as described elsewhere herein, wherein is ; R3, when present, is ; and R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl, –C(O)-heteroalkylene-NR4aR4b, alkyl, –C(O)-alkylene-COOR5, –C(O)-alkylene-C(O)NR4aR4b, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl, wherein R4aand R4bare independently hydrogen, alkyl, or acyl. In certain embodiments, R3ais alkyl; R3bis hydrogen; and R3cis one or more alkoxy or halo. In certain embodiments, R3is , , , , or . In certain embodiments, R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl. In certain embodiments, R4is , , , , or . In certain embodiments, R1is and R9is , or . In certain embodiments, R9is , , or . In certain embodiments, the compound is selected from the group consisting of 3-((2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro- 1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)methyl)-4-fluorobenzoic acid (220), 2-(2-((2- (3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetamido)methyl)thiazol-4-yl)acetic acid (221), 2-(4-((2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro- 1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)methyl)-1H-1,2,3-triazol-1-yl)acetic acid (222), and 2-(4-((2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)- N-methylacetamido)methyl)-1H-1,2,3-triazol-1-yl)acetic acid (226). In one embodiment, the compounds is 3-((2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro- 1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)methyl)-4-fluorobenzoic acid (220). In one embodiment, the compounds is 2-(2-((2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H- [4,6'-biindazol]-1-yl)acetamido)methyl)thiazol-4-yl)acetic acid (221). In one embodiment, the compounds is 2-(4-((2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetamido)methyl)-1H-1,2,3-triazol-1-yl)acetic acid (222). In one embodiment, the compounds is 2-(4-((2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N- methylacetamido)methyl)-1H-1,2,3-triazol-1-yl)acetic acid (226). In certain embodiments, provided is a compound having the following formula or a pharmaceutically acceptable salt thereof as described elsewhere herein, wherein is ; R3, when present, is ; and R4, when present, is hydrogen or a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl, –C(O)-heteroalkylene-NR4aR4b, alkyl, –C(O)-alkylene-COOR5, –C(O)-alkylene-C(O)NR4aR4b, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl, wherein R4aand R4bare independently hydrogen, alkyl, or acyl. In certain embodiments, R3ais alkyl; R3bis hydrogen; and R3cis one or more alkoxy or halo. In certain embodiments, R3is , , embodiments, R4, when present, is hydrogen g y y prising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl. In certain embodiments, R4is hydrogen, , , , , or . In certain embodiments, R1is . In certain embodiments, the compound is selected from the group consisting of (2-(3-(1-acetylpiperidin-4-yl)-7-amino-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (223) and (2-(5'-fluoro-1'-methyl-7-(methylthio)-1H,1'H-[4,6'-biindazol]- 1-yl)acetyl)glycylglycine (224). In one embodiment, the compounds is (2-(3-(1-acetylpiperidin-4- yl)-7-amino-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (223). In one embodiment, the compounds is (2-(5'-fluoro-1'-methyl-7-(methylthio)-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (224). In certain embodiments, provided is a compound having the following formula or a pharmaceutically acceptable salt thereof as described elsewhere herein, wherein ; R3, when present, is or ; and R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl, –C(O)-heteroalkylene-NR4aR4b, alkyl, –C(O)-alkylene-COOR5, –C(O)-alkylene-C(O)NR4aR4b, hetero , cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl, wherei dependently hydrogen alkyl or acyl; or a five- to fifteen-membered spiro b kyl comprising at leas erein the at least one nitrogen is uns uted with alkyl, he , alkynyl, acyl, cycloalkyl, hetero , aryl, arylalkyl, hete alkylene-C(O)R3aaawherein R3aaais –OR7a, –NR7aR7bor alkyl. In certain embodiments, R3ais alkyl; R3bis hydrogen; and R3cis one or more alkoxy, cyano, or halo. In certain embodiments, R3is , , , , , or . In certain embodiments, R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen; or a five- to fifteen-membered spiro bicyclic heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl. In certain embodiments, R4is , , , , , or . In certain emb iments, the compound is selected from the group consisting of N-(2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- l)acetyl)-N-cyclopropylglycylglycine (225), N-(2-(3-(1-acetylpiperidin-4-yl)-5'- yl-1H,2'H-[4,6'-biindazol]-1-yl)acetyl)-N-cyclopropylglycylglycine (227), and N- -2-azaspiro[3.3]heptan-6-yl)-5'-cyano-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)-N-methylglycylglycine (228). In one embodiment, the compound is N-(2-(3-(1- acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N- cyclopropylglycylglycine (225). In one embodiment, the compound is N-(2-(3-(1-acetylpiperidin- 4-yl)-5'-fluoro-2'-methyl-1H,2'H-[4,6'-biindazol]-1-yl)acetyl)-N-cyclopropylglycylglycine (227). In one embodiment, the compound is N-(2-(3-(2-acetyl-2-azaspiro[3.3]heptan-6-yl)-5'-cyano-1'- methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N-methylglycylglycine (228). In certain embodiments, provided is a compound having the following formula or a pharmaceutically acceptable salt thereof as described elsewhere herein, wherein is ; R3, when present, is aryl or heteroaryl, wherein aryl or heteroaryl are unsubstituted or substituted with alkyl, heteroalkyl, heterocycloalkyl, and / or halo; and R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl, –C(O)-heteroalkylene-NR4aR4b, alkyl, –C(O)-alkylene-COOR5, –C(O)-alkylene-C(O)NR4aR4b, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl, wherein R4aand R4bare independently hydrogen, alkyl, or acyl. In certain embodiments, R3is or . In certain embodiments, R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl. In certain embodiments, R4is , , , , or . In certain b di t R1i I t i b di ts, the compound is selected from inolin- 3-yl)-1H-indazol-1-yl)acety methyl- 1H-indol-6-yl)-1H-indazol- ound is (2-(3-(1-acetylpiperidin-4-yl) 4 (isoquinolin 3 yl) 1H indazol 1 yl)acetyl)glycylglycine (230). In one embodiment, the compound is (2-(3-(1-acetylpiperidin-4-yl)-4-(1-methyl-1H-indol-6-yl)-1H- indazol-1-yl)acetyl)glycylglycine (231). In certain embodiments, provided is a compound having the following formula or a pharmaceutically acceptable salt thereof as described elsewhere herein, wherein is ; R3, when present, is ; and R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl, –C(O)-heteroalkylene-NR4aR4b, alkyl, –C(O)-alkylene-COOR5, –C(O)-alkylene-C(O)NR4aR4b, –C(O)-alkylene-C(O)N(R4a)-heteroalkylene-halo, heteroalkyl, alkenyl, alkynyl, cycloalkyl, alkyl, haloalkyl, aryl, arylalkyl, or heteroaryl, wherein R4aand R4bare independently lkyl, or acyl. In certain embodiments, R3ais alkyl; R3bis hydrogen; and R3cis one or more alkoxy or halo. In certain embodiments, R3is , , , , or . In certain embodiments, R4, when present, is a three- to eight- membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with –C(O)-alkylene-C(O)N(R4a)-heteroalkylene-halo wherein R4ais hydrogen, alkyl, or acyl. In certain embodiments, R4is selected from the group consisting of , , , and . In certain embodiments, R1is . In certain embodiments, the compound is selected from the group consisting of (2-(3-(1-(20-chloro-4-oxo-8,11,14-trioxa-5-azaicosanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl- 1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (232), methyl (2-(3-(1-(20-chloro-4-oxo- 8,11,14-trioxa-5-azaicosanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (233), (2-(3-(1-(23-chloro-4-oxo-8,11,14,17-tetraoxa-5- azatricosanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (234), methyl (2-(3-(1-(23-chloro-4-oxo-8,11,14,17-tetraoxa-5- azatricosanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (235), (2-(3-(1-(26-chloro-4-oxo-8,11,14,17,20-pentaoxa-5- azahexacosanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- ycine (236), methyl (2-(3-(1-(26-chloro-4-oxo-8,11,14,17,20-pentaoxa-5- piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- ycinate (237), (2-(3-(1-(29-chloro-4-oxo-8,11,14,17,20,23-hexaoxa-5- azanonacosanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glyc nd methyl (2-(3-(1-(29-chloro-4-oxo-8,11,14,17,20,23-hexaoxa-5- azanonacosan )-5'-fluoro-1'-methyl-1H,1'H yl)acetyl)glyc ent, the compound is (2-(3-( ,11,14-trioxa-5- azaicosanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (232). In one embodiment, the compound is methyl (2-(3-(1-(20-chloro-4- oxo-8,11,14-trioxa-5-azaicosanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (233). In one embodiment, the compound is (2-(3-(1-(23-chloro-4-oxo- 8,11,14,17-tetraoxa-5-azatricosanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]- 1-yl)acetyl)glycylglycine (234). In one embodiment, the compound is methyl (2-(3-(1-(23-chloro- 4-oxo-8,11,14,17-tetraoxa-5-azatricosanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)acetyl)glycylglycinate (235). In one embodiment, the compound is (2-(3-(1-(26- chloro-4-oxo-8,11,14,17,20-pentaoxa-5-azahexacosanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl- 1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (236). In one embodiment, the compound is methyl (2-(3-(1-(26-chloro-4-oxo-8,11,14,17,20-pentaoxa-5-azahexacosanoyl)piperidin-4-yl)-5'- fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (237). In one embodiment, the compound is (2-(3-(1-(29-chloro-4-oxo-8,11,14,17,20,23-hexaoxa-5- azanonacosanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (238). In one embodiment, the compound is methyl (2-(3-(1-(29-chloro-4- oxo-8,11,14,17,20,23-hexaoxa-5-azanonacosanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H- [4,6'-biindazol]-1-yl)acetyl)glycylglycinate (239). In certain embodiments, provided is a compound having the following formula embodiment, the compound is (S)-5-(2-fluoro-6-hydroxypyridin-3-yl)-N-methyl-2-((1-(3-((1- methyl-1H-tetrazol-5-yl)methoxy)benzoyl)piperidin-3-yl)methoxy)benzamide (240). In one embodiment, the compound is (R)-5-(2-fluoro-6-hydroxypyridin-3-yl)-N-methyl-2-((1-(3-((1- methyl-1H-tetrazol-5-yl)methoxy)benzoyl)piperidin-3-yl)methoxy)benzamide (241). In one embodiment, the compound is (S)-5-(2-fluoro-6-hydroxypyridin-3-yl)-N-methyl-2-((4-(3-((1- methyl-1H-tetrazol-5-yl)methoxy)benzoyl)morpholin-2-yl)methoxy)benzamide (242). In one embodiment, the compound is (R)-5-(2-fluoro-6-hydroxypyridin-3-yl)-N-methyl-2-((4-(3-((1- methyl-1H-tetrazol-5-yl)methoxy)benzoyl)morpholin-2-yl)methoxy)benzamide (243). In certain embodiments, provided is a compound having the following formula or a pharmaceutically acceptable salt thereof as described elsewhere herein, wherein the compound is N-(2-(2-(2-(2- aminoethoxy)ethoxy)ethoxy)ethyl)-6-(4-(2-(1-(2-(3,5- dioxomorpholino)acetamido)cyclobutyl)acetamido)piperidin-1-yl)nicotinamide (244). In certain embodiments, provided is a compound having the following formula or a pharmaceutically acceptable salt thereof as described elsewhere herein, wherein the compound is N-(2-(2-(2-(2- aminoethoxy)ethoxy)ethoxy)ethyl)-5-((2-(3,5-dioxomorpholino)-N-(imidazo[2,1-b]thiazol-3- ylmethyl)acetamido)methyl)-2,4-dimethylbenzamide (245).Pharmaceutical CompositionsThe compounds described herein can be formulated into pharmaceutical compositions that further comprise a pharmaceutically acceptable carrier, diluent, adjuvant, or vehicle. In one embodiment, this disclosure provides a pharmaceutical composition comprising one or more compounds described herein, and a pharmaceutically acceptable carrier, diluent, adjuvant, or vehicle. In one embodiment, this disclosure provides a pharmaceutical composition comprising an effective amount of one or more compounds of this disclosure, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, diluent, adjuvant, or vehicle. Pharmaceutically acceptable carriers include, for example, pharmaceutical diluents, excipients, or carriers suitably selected with respect to the intended form of administration, and consistent with conventional pharmaceutical practices. According to another embodiment, this description provides a composition comprising one or more compounds herein, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle. Pharmaceutical compositions of this description comprise a therapeutically effective amount of one or more compounds of the formula , wherein a “therapeutically effective amount” is an amount that is (a) effective to modulate KLHDC1 and / or KLHDC2 activity in a biological sample or in a patient; or (b) effective in treating and / or ameliorating a disease or disorder that is mediated by KLHDC1 and / or KLHDC2. It will also be appreciated that certain compounds of this disclosure can exist in free form (e.g., a neutral compound) for treatment, or where appropriate, as a pharmaceutically acceptable derivative (e.g., a salt) thereof. According to this disclosure, a pharmaceutically acceptable derivative includes, but is not limited to, pharmaceutically acceptable prodrugs, salts, esters, salts of such esters, or any other adduct / educt or derivative that upon administration to a patient in need is capable of providing, directly or indirectly, one or more compounds as otherwise described herein, or a metabolite, or residue thereof. As used herein, the term “pharmaceutically acceptable salt” refers to those salts that are, within the scope of sound medical practice or judgment, suitable for use in contact with cells, tissues, and / or the tissues of humans and lower animals without undue toxicity, irritation, allergic response, and the like. Pharmaceutically acceptable salts are well known in the art. For example, S. M. Berge et al. describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences 1977, 66, 1-19, incorporated herein by reference. Pharmaceutically acceptable salts of the compounds of this description include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable, nontoxic acid addition salts include salts of an amino group formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid; or with organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid; or by using other methods used in the art such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, and valerate salts, and the like. Salts derived from appropriate bases include alkali metal, alkaline earth metal, ammonium (NH4+), and N+(C1-4 alkyl)4 salts. This description also envisions the quaternization of any basic nitrogen-containing groups of the compounds disclosed herein. Water or oil-soluble or dispersable products may be obtained by such quaternization. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Further pharmaceutically acceptable salts include, when appropriate, nontoxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, lower alkyl sulfonate, and aryl sulfonate. A pharmaceutically acceptable carrier may contain inert ingredients that do not unduly inhibit the biological activity of the compounds described herein. The pharmaceutically acceptable carriers should be biocompatible, for example, non-toxic, non-inflammatory, non- immunogenic, and / or devoid of other undesired reactions or side-effects upon administration to a subject. Standard pharmaceutical formulation techniques can be employed. The pharmaceutically acceptable carrier, adjuvant, or vehicle, as used herein, includes any and all solvents, diluents, or other liquid vehicle, dispersion, or suspension aids, surface active agents, isotonic agents, thickening or emulsifying agents, preservatives, solid binders, lubricants, and the like, as suited to the particular dosage form desired. Remington’s Pharmaceutical Sciences, Sixteenth Edition, E. W. Martin (Mack Publishing Co., Easton, Pa., 1980) discloses various carriers used in formulating pharmaceutically acceptable compositions, and known techniques for the preparation thereof. Except insofar as any conventional carrier medium is incompatible with the compounds described herein, such as by producing any undesirable biological effect, or otherwise interacting in a deleterious manner with any other component(s) of the pharmaceutically acceptable composition, the use of such conventional carrier medium is contemplated to be within the scope of this description. As used herein, the phrase “side effects” encompasses unwanted and adverse effects of a therapy (e.g., a prophylactic or therapeutic agent). Side effects are usually unwanted, but unwanted effects are not necessarily adverse or unbeneficial. An adverse effect from a therapy (e.g., prophylactic or therapeutic agent) might be harmful, uncomfortable, or risky. Side effects include, but are not limited to, fever, chills, lethargy, gastrointestinal toxicities (including gastric and intestinal ulcerations and erosions), nausea, vomiting, neurotoxicities, nephrotoxicities or renal toxicities (including such conditions as papillary necrosis and chronic interstitial nephritis), hepatic toxicities (including elevated serum liver enzyme levels), myelotoxicities (including leukopenia, myelosuppression, thrombocytopenia, and anemia), dry mouth, metallic taste, prolongation of gestation, weakness, somnolence, pain (including muscle pain, bone pain, and headache), hair loss, asthenia, dizziness, extra-pyramidal symptoms, akathisia, cardiovascular disturbances, and sexual dysfunction. Some examples of materials that can serve as pharmaceutically acceptable carriers include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, serum proteins (such as human serum albumin), buffer substances (such as Tween 80, phosphates, glycine, sorbic acid, or potassium sorbate), partial glyceride mixtures of saturated vegetable fatty acids, water, salts or electrolytes (such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, or zinc salts), colloidal silica, magnesium trisilicate, polyvinyl pyrrolidone, polyacrylates, waxes, polyethylene-polyoxypropylene-block polymers, methylcellulose, hydroxypropyl methylcellulose, wool fat, sugars such as lactose, glucose, and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethyl cellulose, ethyl cellulose, and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; glycols such as propylene glycol or polyethylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffering agents such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen- free water; isotonic saline; Ringer’s solution; ethyl alcohol, and phosphate buffer solutions, as well as other non-toxic compatible lubricants such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, releasing agents, coating agents, sweetening, flavoring, and perfuming agents. Preservatives and antioxidants can also be present in the composition, according to the judgment of the formulator.AdministrationThe compositions of this disclosure may be administered orally, parenterally, via inhalation spray, topically, rectally, nasally, buccally, vaginally, or via an implanted reservoir. As used herein, the term “parenteral” includes subcutaneous, intravenous, intramuscular, intra- articular, intra-synovial, intrasternal, intrathecal, intraocular, intrahepatic, intralesional, and intracranial injection or infusion techniques. Compositions can be administered orally, intraperitoneally, or intravenously. Sterile injectable forms of the compositions of this disclosure may be aqueous or oleaginous suspension. These suspensions may be formulated according to techniques known in the art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally-acceptable diluent or solvent, for example, as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution, and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose, any bland fixed oil may be employed including synthetic mono- or di-glycerides. Fatty acids, such as oleic acid and its glyceride derivatives, are useful in the preparation of injectables, as are natural pharmaceutically acceptable oils, such as olive oil or castor oil, especially in their polyoxyethylated versions. These oil solutions or suspensions may also contain a long-chain alcohol diluent or dispersant, such as carboxymethyl cellulose or similar dispersing agents that are commonly used in the formulation of pharmaceutically acceptable dosage forms including emulsions and suspensions. Other commonly used surfactants, such as Tweens, Spans, and other emulsifying agents or bioavailability enhancers that are commonly used in the manufacture of pharmaceutically acceptable solid, liquid, or other dosage forms may also be used for the purposes of formulation. The pharmaceutically acceptable compositions of this disclosure may be orally administered in any orally acceptable dosage form including, but not limited to, capsules, tablets, aqueous suspensions, or solutions. In the case of tablets for oral use, carriers commonly used include lactose and corn starch. Lubricating agents, such as magnesium stearate, are also typically added. For oral administration in a capsule form, useful diluents include lactose and dried cornstarch. When aqueous suspensions are required for oral use, the active ingredient is combined with emulsifying and suspending agents. If desired, certain sweetening, flavoring, or coloring agents may also be added. Alternatively, the pharmaceutically acceptable compositions of this disclosure may be administered in the form of suppositories for rectal or vaginal administration. These can be prepared by mixing the agent with a suitable non-irritating excipient that is solid at room temperature but liquid at rectal or vaginal temperature and therefore will melt in the rectum or vaginal cavity to release the drug. Such materials include cocoa butter, polyethylene glycol, or a suppository wax that is solid at ambient temperature but liquid at body temperature and therefore melts in the rectum or vaginal cavity and releases the active compound. The pharmaceutically acceptable compositions of this disclosure may also be administered topically, especially when the target of treatment includes areas or organs readily accessible by topical application, including diseases of the eye, skin, or lower intestinal tract. Suitable topical formulations are readily prepared for each of these areas or organs. Topical application for the lower intestinal tract can be via a rectal suppository formulation (see above) or in a suitable enema formulation. Topically-transdermal patches may also be used. For topical applications, the pharmaceutically acceptable compositions may be formulated in a suitable ointment containing the active component suspended or dissolved in one or more carriers. Carriers for topical administration of the compounds of this disclosure include, but are not limited to, mineral oil, liquid petrolatum, white petrolatum, propylene glycol, polyoxyethylene, polyoxypropylene compound, emulsifying wax, and water. Alternatively, the pharmaceutically acceptable compositions can be formulated in a suitable lotion or cream containing the active components suspended or dissolved in one or more pharmaceutically acceptable carriers. Suitable carriers include, but are not limited to, mineral oil, sorbitan monostearate, polysorbate 60, cetyl esters wax, cetearyl alcohol, 2-octyldodecanol, benzyl alcohol, and water. For ophthalmic use, the pharmaceutically acceptable compositions may be formulated, for example, as micronized suspensions in isotonic, pH adjusted sterile saline or other aqueous solution, or as solutions in isotonic, pH adjusted sterile saline or other aqueous solution, either with or without a preservative such as benzylalkonium chloride. Alternatively, for ophthalmic uses, the pharmaceutically acceptable compositions may be formulated in an ointment such as petrolatum. The pharmaceutically acceptable compositions of this disclosure may also be administered by nasal aerosol or inhalation. Such compositions are prepared according to techniques well-known in the art of pharmaceutical formulation and may be prepared as solutions in saline, employing benzyl alcohol or other suitable preservatives, absorption promoters to enhance bioavailability, fluorocarbons, and / or other conventional solubilizing or dispersing agents. In certain embodiments, the compositions of this disclosure are administered orally. The pharmaceutically acceptable compositions of this description may be orally administered in any orally acceptable dosage form including, but not limited to, capsules, tablets, aqueous suspensions, or solutions. In the case of tablets for oral use, carriers commonly used include lactose and corn starch. Lubricating agents, such as magnesium stearate, are also typically added. For oral administration in a capsule form, useful diluents include lactose and dried cornstarch. When aqueous suspensions are required for oral use, the active ingredient is combined with emulsifying and suspending agents. If desired, certain sweetening, flavoring, or coloring agents may also be added. Liquid dosage forms for oral administration include, but are not limited to, pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups, and elixirs. In addition to the biologically active compounds herein, the liquid dosage forms may contain inert diluents commonly used in the art, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. Besides inert diluents, the oral compositions can also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents. Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the biologically active compound(s) described herein are mixed with at least one inert, pharmaceutically acceptable excipient or carrier such as sodium citrate or dicalcium phosphate, and / or a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol, and silicic acid; b) binders such as carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidinone, sucrose, and acacia; c) humectants such as glycerol; d) disintegrating agents such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate; e) solution retarding agents such as paraffin; f) absorption accelerators such as quaternary ammonium compounds; g) wetting agents, for example, cetyl alcohol and glycerol monostearate; h) absorbents such as kaolin and bentonite clay; and i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. In the case of capsules, tablets, and pills, the dosage form may also comprise buffering agents. Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like. The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings and other coatings well known in the pharmaceutical formulating art. Solid dosage forms optionally may contain opacifying agents. These solid dosage forms can also be of a composition such that they release the active ingredient(s) only, for example, in a certain part of the intestinal tract, optionally in a delayed manner. Examples of embedding compositions that can be used include polymeric substances and waxes. Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polethylene glycols and the like. The active compounds herein can also be in micro-encapsulated form with one or more excipients as noted above. The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings, release controlling coatings, and other coatings well known in the pharmaceutical formulating art. In such solid dosage forms the active compound may be admixed with at least one inert diluent such as sucrose, lactose, or starch. Such dosage forms may also comprise, as is normal practice, additional substances other than inert diluents, for example, tableting lubricants and other tableting aids such a magnesium stearate and microcrystalline cellulose. In the case of capsules, tablets, and pills, the dosage forms may also comprise buffering agents. They may optionally contain opacifying agents and can also be of a composition such that they release the active ingredient(s) only, for example, in a certain part of the intestinal tract, optionally in a delayed manner. Examples of embedding compositions that can be used include polymeric substances and waxes. The compounds of the description are formulated in dosage unit form for ease of administration and uniformity of dosage. As used herein, the phrase “dosage unit form” refers to a physically discrete unit of agent appropriate for the subject, cell, tissue, or patient to be treated. It will be understood, however, that the total daily usage of the compounds, and compositions of this disclosure will be decided by the attending physician within the scope of sound medical judgment. The specific effective dose level for any particular subject, cell, tissue, patient, or organism will depend upon a variety of factors including the disorder being treated and the severity of the disorder; the activity of the specific compound(s) employed; the specific composition(s) employed; the age, body weight, general health, sex, and diet of the subject, cell, tissue, and / or patient; the time of administration, route of administration, and rate of excretion of the specific compound(s) employed; the duration of the treatment; drugs used in combination or coincidental with the specific compound(s) employed, and like factors well known in the medical arts. The amount of the compounds of this disclosure that may be combined with the carrier materials to produce a composition in a single dosage form will vary depending upon the subject, cell, tissue, and / or host treated, the particular mode of administration, and other factors. The compositions should be formulated so that a dosage of between 0.01 - 100 mg / kg body weight / day of the compound(s) or inhibitor(s) can be administered to a subject, cell, tissue, and / or patient receiving these compositions. Depending upon the particular condition or disease to be treated or prevented, additional therapeutic agents, which are normally administered to treat or prevent that condition, may also be present in the compositions of this disclosure. As used herein, additional therapeutic agents that are normally administered to treat or prevent a particular disease, or condition, are known as “appropriate for the disease, or condition, being treated.” The compound or composition can be administered concurrently with, prior to, or subsequent to, one or more additional therapeutically active agents. In general, each agent will be administered at a dose and / or on a time schedule determined for that agent. It will further be appreciated that the additional therapeutically active agent utilized in this combination can be administered together in a single composition or administered separately in different composition. The particular combination to employ in a regimen will take into account compatibility of the compounds described herein with the additional therapeutically active agent and / or the desired therapeutic effect to be achieved. In general, it is expected that additional therapeutically active agents utilized in combination will be utilized at levels that do not exceed the levels at which they are utilized individually. In some embodiments, the levels utilized in combination will be lower than those utilized individually. Additional therapeutically active agents include, but are not limited to, small organic molecules such as drug compounds (e.g., compounds approved by the Food and Drug Administration as provided in the Code of Federal Regulations (CFR)), peptides, proteins, carbohydrates, monosaccharides, oligosaccharides, polysaccharides, nucleoproteins, mucoproteins, lipoproteins, synthetic polypeptides or proteins, small molecules linked to proteins, glycoproteins, steroids, nucleic acids, DNAs, RNAs, nucleotides, nucleosides, oligonucleotides, antisense oligonucleotides, lipids, hormones, vitamins, and cells. In certain embodiments, the additional therapeutically active agent is a cancer agent (e.g., a biotherapeutic or chemo therapeutic cancer agent). In other embodiments, the additional therapeutically active agent is an anti- inflammatory agent. The amount of additional therapeutic agent present in the compositions of this disclosure will be no more than the amount that would normally be administered in a composition comprising that therapeutic agent as the only active agent. The amount of additional therapeutic agent in the presently disclosed compositions will range from about 50% to 100% of the amount normally present in a composition comprising that agent as the only therapeutically active agent.Methods of UseThe compounds described herein are useful for inhibiting or modulating KLHDC1 or KLHDC2 in biological samples, or in patients. Thus, an embodiment of this disclosure provides a method of treating a disease or disorder via modulating KLHDC1 or KLHDC2 activity. As used herein, the term “KLHDC1- or KLHDC2-mediated disease or disorder” means any disease, disorder, or other deleterious condition in which KLHDC1 or KLHDC2 is known to play a role. In some instances, an KLHDC1- or KLHDC2-mediated disease or disorder is a proliferative disorder or an autoimmune disorder. Examples of proliferative disorders include cancer. In one aspect, provided herein are methods of treating or preventing cancer in a subject in need thereof. In certain embodiments, the methods comprise the step of orally administering to the subject an amount of a compounds(s) described herein capable of modulating KLHDC1 or KLHDC2 activity. In certain embodiments, the amount is effective to treat or prevent the cancer. In certain embodiments, the cancer is any cancer described below. In particular embodiments, the cancer comprises a solid tumor. In certain embodiments, the cancer is a B cell malignancy. In certain embodiments, the cancer is selected from the group consisting of chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), transformed CLL or Richter’s transformation, small cell lymphoma, follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), non-Hodgkin lymphoma, mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), Waldenstrom macroglobulinemia (WM), and central nervous system (CNS) lymphoma. In certain embodiments, the cancer is chronic lymphocytic leukemia. In certain embodiments, the cancer is small cell lymphoma. In certain embodiments, the cancer is follicular lymphoma. In certain embodiments, the cancer is diffuse large B-cell lymphoma. In certain embodiments, the cancer is non-Hodgkin lymphoma. In certain embodiments, the cancer is mantle cell lymphoma. In certain embodiments, the cancer is marginal zone lymphoma. In certain embodiments, the cancer is Waldenstrom macroglobulinemia. In certain embodiments, the cancer is small lymphocytic lymphoma (SLL). In certain embodiments, the cancer is CNS lymphoma. In certain embodiments, the cancer is transformed CLL or Richter’s transformation. In certain embodiments, the cancer is chronic lymphocytic leukemia (CLL). In another aspect, provided herein are methods of inhibiting or modulating KLHDC1 or KLHDC2 in a subject in need thereof. The methods comprise the step of orally administering to the subject an amount of a compound(s) described herein and capable of modulating KLHDC1 or KLHDC2. In certain embodiments, the amount is effective to inhibit KLHDC1 or KLHDC2 in the subject. In certain embodiments, the amount is effective to modulate KLHDC1 or KLHDC2 in the subject. The KLHDC1 or KLHDC2 can be expressed in any cells or tissues of the subject. The compound(s) described herein can be administered in any dose deemed suitable by the practitioner of skill. In certain embodiments, the dose is 0.1-1000 mg / kg. In certain embodiments, the dose is 0.1-900 mg / kg. In certain embodiments, the dose is 0.1-800 mg / kg. In certain embodiments, the dose is 0.1-700 mg / kg. In certain embodiments, the dose is 0.1-600 mg / kg. In certain embodiments, the dose is 0.1-500 mg / kg. In certain embodiments, the dose is 0.1-400 mg / kg. In certain embodiments, the dose is 0.1-300 mg / kg. In certain embodiments, the dose is 0.1-200 mg / kg. In certain embodiments, the dose is 0.1-100 mg / kg. In certain embodiments, the dose is selected from the group consisting of 100 mg / kg, 200 mg / kg, 300 mg / kg, 450 mg / kg, 600 mg / kg, 800 mg / kg, and 1000 mg / kg. In certain embodiments, the dose is about 25 mg / kg. In certain embodiments, the dose is about 50 mg / kg. In certain embodiments, the dose is about 75 mg / kg. In certain embodiments, the dose is about 100 mg / kg. In certain embodiments, the dose is about 150 mg / kg. In certain embodiments, the dose is about 200 mg / kg. In certain embodiments, the dose is about 250 mg / kg. In certain embodiments, the dose is about 300 mg / kg. In certain embodiments, the dose is about 400 mg / kg. In certain embodiments, the dose is about 450 mg / kg. In certain embodiments, the dose is about 500 mg / kg. In certain embodiments, the dose is about 600 mg / kg. In certain embodiments, the dose is about 700 mg / kg. In certain embodiments, the dose is about 750 mg / kg. In certain embodiments, the dose is about 800 mg / kg. In certain embodiments, the dose is about 900 mg / kg. In certain embodiments, the dose is about 1000 mg / kg. The dose can be administered on a schedule deemed suitable by the person of skill in the art. In certain embodiments, the dose is administered once per day. In certain embodiments, the dose is administered twice per day. In certain embodiments, the dose is administered three times per day. In certain embodiments, the dose is administered four times per day. In certain embodiments, the dose is administered in divided doses. In certain embodiments, the dose is administered in two divided doses per day. In certain embodiments, the dose is administered in three divided doses per day. In certain embodiments, the dose is administered in four divided doses per day. Dosing can continue for any length of time deemed suitable by the person of skill in the art. In certain embodiments, the dose is administered daily for fourteen days. In certain embodiments, the dose is administered daily for thirteen days. In certain embodiments, the dose is administered daily for twelve days. In certain embodiments, the dose is administered daily for eleven days. In certain embodiments, the dose is administered daily for ten days. In certain embodiments, the dose is administered daily for nine days. In certain embodiments, the dose is administered daily for eight days. In certain embodiments, the dose is administered daily for seven days. In certain embodiments, the dose is administered daily for six days. In certain embodiments, the dose is administered daily for five days. In certain embodiments, the dose is administered daily for four days. In certain embodiments, the dose is administered daily for three days. In certain embodiments, the dose is administered daily for two days. In certain embodiments, the dose is administered for one day. In the dosing schedule, the doses can be administered on consecutive days or cyclicly, according to the judgment of the practitioner of skill. In certain embodiments, the doses are administered on consecutive days. In certain embodiments, the doses are administered with an interval between doses. In certain embodiments, the interval is one day. In certain embodiments, the interval is two days. In certain embodiments, the interval is three days. In certain embodiments, the interval is four days. In certain embodiments, the interval is five days. In certain embodiments, the interval is six days. In certain embodiments, the dose is administered weekly. In certain embodiments, the dose is administered twice per week. In certain embodiments, the dose is administered three times per week. In certain embodiments, the dose(s) are administered for a period of time with a first interval between dose(s), and then the dose(s) are re-administered for a period of time following the first interval between dose(s), wherein this dosing regimen can be repeated (i.e., cyclicly or cyclically, for example, after a second, third, etc. interval between subsequent administrations of dose(s)) according to the judgment of the practitioner of skill. For example, in one embodiment, a first dose is administered for one week, followed by a first interval of one week without the first dose administration; then, a second dose is re-administered for another week, followed by a second interval of one week without the first or second dose administration, and so on cyclically. Other perturbations for first, second, third, etc. dose(s) followed by perturbations for first, second, third, etc. interval(s), and combinations thereof, are contemplated herein as would be appreciated by the practitioner of skill and the need of the subject, cell, tissue, and / or patient. For example, in one embodiment, a first dose is administered daily for one week, followed by a first interval of three weeks without the first daily dose administration; then, a second dose is re- administered biweekly for another week, followed by a second interval of four weeks without the first daily or second biweekly dose administration, and so on cyclically. The compound can be administered by any route of administration deemed suitable by the practitioner of skill. In certain embodiments, the dose is administered orally. Formulations and techniques for administration are described elsewhere herein. In certain embodiments, term “cancer” includes, but is not limited to, the following cancers: epidermoid Oral: buccal cavity, lip, tongue, mouth, pharynx, squamous cell carcinoma of the head and neck (HNSCC); Cardiac: sarcoma (angiosarcoma, fibrosarcoma, rhabdomyosarcoma, liposarcoma), myxoma, rhabdomyoma, fibroma, lipoma, and teratoma; Lung: bronchogenic carcinoma (squamous cell or epidermoid, undifferentiated small cell, undifferentiated large cell, adenocarcinoma), alveolar (bronchiolar) carcinoma, bronchial adenoma, sarcoma, lymphoma, chondromatous hamartoma, mesothelioma, non-small cell lung cancer (NSCLC); Gastrointestinal: gastric cancer, esophagus (squamous cell carcinoma, larynx, adenocarcinoma, leiomyosarcoma, lymphoma), stomach (carcinoma, lymphoma, leiomyosarcoma), pancreas (ductal adenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumors, vipoma), small bowel or small intestines (adenocarcinoma, lymphoma, carcinoid tumors, Karposi’s sarcoma, leiomyoma, hemangioma, lipoma, neurofibroma, fibroma), large bowel or large intestines (adenocarcinoma, tubular adenoma, villous adenoma, hamartoma, leiomyoma), colon, colon- rectum, colorectal, microsatellite stable colorectal cancer (MSS CRC), rectum; Genitourinary tract: kidney (adenocarcinoma, Wilm’s tumor (nephroblastoma), lymphoma, leukemia), bladder and urethra (squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma), prostate (adenocarcinoma, sarcoma), testis (seminoma, teratoma, embryonal carcinoma, teratocarcinoma, choriocarcinoma, sarcoma, interstitial cell carcinoma, fibroma, fibroadenoma, adenomatoid tumors, lipoma), metastatic castrate-resistant prostate cancer (mCRPC), muscle-invasive urothelial cancer; Liver: hepatoma (hepatocellular carcinoma), cholangiocarcinoma, hepatoblastoma, angiosarcoma, hepatocellular adenoma, hemangioma, biliary passages; Bone: osteogenic sarcoma (osteosarcoma), fibrosarcoma, malignant fibrous histiocytoma, chondrosarcoma, Ewing’s sarcoma, malignant lymphoma (reticulum cell sarcoma), multiple myeloma (MM), malignant giant cell tumor chordoma, osteochronfroma (osteocartilaginous exostoses), benign chondroma, chondroblastoma, chondromyxofibroma, osteoid osteoma and giant cell tumors; Nervous system: skull (osteoma, hemangioma, granuloma, xanthoma, osteitis deformans), meninges (meningioma, meningiosarcoma, gliomatosis), brain (astrocytoma, medulloblastoma, glioma, ependymoma, germinoma (pinealoma), glioblastoma multiform, oligodendroglioma, schwannoma, retinoblastoma, congenital tumors), spinal cord neurofibroma, meningioma, glioma, sarcoma); Gynecological: uterus (endometrial carcinoma), cervix (cervical cancer, cervical carcinoma, pre-tumor cervical dysplasia), ovaries (ovarian carcinoma (serous cystadenocarcinoma, mucinous cystadenocarcinoma, unclassified carcinoma), granulosa-thecal cell tumors, Sertoli-Leydig cell tumors, dysgerminoma, malignant teratoma), vulva (squamous cell carcinoma, intraepithelial carcinoma, adenocarcinoma, fibrosarcoma, melanoma), vagina (clear cell carcinoma, squamous cell carcinoma, botryoid sarcoma (embryonal rhabdomyosarcoma), fallopian tubes (carcinoma), breast, triple-negative breast cancer (TNBC), platinum-resistant epithelial ovarian cancer (EOC); Hematologic: blood (myeloid leukemia (acute and chronic), acute lymphoblastic leukemia, chronic lymphocytic leukemia, myeloproliferative diseases, multiple myeloma, myelodysplastic syndrome), Hodgkin’s disease, non-Hodgkin’s lymphoma (malignant lymphoma) hairy cell; lymphoid disorders (e.g., mantle cell lymphoma, Waldenström’s macroglobulinemia, Marginal zone lymphoma, and Follicular lymphoma); Skin: malilymphgnant melanoma, basal cell carcinoma, squamous cell carcinoma, Karposi’s sarcoma, keratoacanthoma, moles or dysplastic nevi, lipoma, angioma, dermatofibroma, keloids, psoriasis; Thyroid gland: papillary thyroid carcinoma, follicular thyroid carcinoma; medullary thyroid carcinoma, undifferentiated thyroid cancer, multiple endocrine neoplasia type 2A, multiple endocrine neoplasia type 2B, familial medullary thyroid cancer, pheochromocytoma, paraganglioma; Adrenal glands: neuroblastoma; and metatstaic melanoma. In certain embodiments, the term “autoimmune disease” includes, but is not limited to, the following autoimmune diseases: uticaria, graft-versus-host disease (GVHD), acute graft- versus-host disease, pemphigus vulgaris, achalasia, Addison’s disease, Adult Still’s disease, agammaglobulinemia, alopecia areata, amyloidosis, ankylosing spondylitis, anti-GBM / anti-TBM nephritis, antiphospholipid syndrome, autoimmune angioedema, autoimmune dysautonomia, autoimmune encephalomyelitis, autoimmune hepatitis, autoimmune inner ear disease (AIED), autoimmune myocarditis, autoimmune oophoritis, autoimmune orchitis, autoimmune pancreatitis, autoimmune retinopathy, axonal and neuronal neuropathy (AMAN), Baló disease, Behcet’s disease, benign mucosal pemphigoid, bullous pemphigoid, Castleman disease (CD), Celiac disease, Chagas disease, chronic inflammatory demyelinating polyneuropathy (CIDP), chronic recurrent multifocal osteomyelitis (CRMO), Churg-Strauss Syndrome (CSS) or Eosinophilic Granulomatosis (EGPA), cicatricial pemphigoid, Cogan’s syndrome, cold agglutinin disease, congenital heart block, coxsackie myocarditis, CREST syndrome, Crohn’s disease, dermatitis herpetiformis, dermatomyositis, Devic’s disease (neuromyelitis optica), discoid lupus, Dressler’s syndrome, endometriosis, eosinophilic esophagitis (EoE), eosinophilic fasciitis, erythema nodosum, essential mixed cryoglobulinemia, Evans syndrome, fibromyalgia, fibrosing alveolitis, giant cell arteritis (temporal arteritis), giant cell myocarditis, glomerulonephritis, Goodpasture’s syndrome, granulomatosis with polyangiitis, Graves’ disease, Guillain-Barre syndrome, Hashimoto’s thyroiditis, hemolytic anemia, Henoch-Schonlein purpura (HSP), herpes gestationis or pemphigoid gestationis (PG), hidradenitis suppurativa (HS) (Acne Inversa), hypogammalglobulinemia, IgA nephropathy, IgG4-related sclerosing disease, immune thrombocytopenic purpura (ITP), inclusion body myositis (IBM), interstitial cystitis (IC), juvenile arthritis, juvenile diabetes (Type 1 diabetes), juvenile myositis (JM), Kawasaki disease, Lambert- Eaton syndrome, leukocytoclastic vasculitis, lichen planus, lichen sclerosus, ligneous conjunctivitis, linear IgA disease (LAD), lupus, lyme disease (chronic), Meniere’s disease, microscopic polyangiitis (MPA), mixed connective tissue disease (MCTD), Mooren’s ulcer, Mucha-Habermann disease, Multifocal Motor Neuropathy (MMN) or MMNCB, multiple sclerosis, myasthenia gravis, myositis, narcolepsy, neonatal lupus, neuromyelitis optica, neutropenia, ocular cicatricial pemphigoid, optic neuritis, palindromic rheumatism (PR), PANDAS, paraneoplastic cerebellar degeneration (PCD), paroxysmal nocturnal hemoglobinuria (PNH), Parry Romberg syndrome, pars planitis (peripheral uveitis), Parsonnage-Turner syndrome, pemphigus, peripheral neuropathy, perivenous encephalomyelitis, pernicious anemia (PA), POEMS syndrome, polyarteritis nodosa, polyglandular syndromes type I, II, or III, polymyalgia rheumatica, polymyositis, postmyocardial infarction syndrome, postpericardiotomy syndrome, primary biliary cirrhosis, primary sclerosing cholangitis, progesterone dermatitis, psoriasis, psoriatic arthritis, pure red cell aplasia (PRCA), pyoderma gangrenosum, Raynaud’s phenomenon, reactive arthritis, reflex sympathetic dystrophy, relapsing polychondritis, restless legs syndrome (RLS), retroperitoneal fibrosis, rheumatic fever, rheumatoid arthritis, sarcoidosis, Schmidt syndrome, scleritis, scleroderma, Sjögren’s syndrome, sperm and testicular autoimmunity, stiff person syndrome (SPS), subacute bacterial endocarditis (SBE), Susac’s syndrome, sympathetic ophthalmia (SO), Takayasu’s arteritis, temporal arteritis (giant cell arteritis), thrombocytopenic purpura (TTP), Tolosa-Hunt syndrome (THS), transverse myelitis, Type 1 diabetes, ulcerative colitis (UC), undifferentiated connective tissue disease (UCTD), uveitis, vasculitis, vitiligo, Vogt- Koyanagi-Harada Disease, and Wegener’s granulomatosis (or Granulomatosis with Polyangiitis (GPA)). In certain embodiments, the term “inflammatory disease” includes, but is not limited to, the following inflammatory diseases: encephalitis, myelitis, meningitis, arachnoiditis, neuritis, dacryoadenitis, scleritis, episcleritis, keratitis, retinitis, chorioretinitis, blepharitis, conjunctivitis, uveitis, otitisexterna, otitismedia, labyrinthitis, mastoiditis, endocarditis, myocarditis, pericarditis, vasculitis, arteritis, phlebitis, capillaritis, sinusitis, rhinitis, pharyngitis, laryngitis, tracheitis, bronchitis, bronchiolitis, pneumonitis, pleuritis, mediastinitis, stomatitis, gingivitis, gingivostomatitis, glossitis, tonsillitis, sialadenitis / parotitis, cheilitis, pulpitis, gnathitis, esophagitis, gastritis, gastroenteritis, enteritis, colitis, enterocolitis, duodenitis, ileitis, caecitis, appendicitis, proctitis, hepatitis, ascendingcholangitis, cholecystitis, pancreatitis, peritonitis, dermatitis, folliculitis, cellulitis, hidradenitis, arthritis, dermatomyositis, myositis, synovitis / tenosynovitis, bursitis, enthesitis, fasciitis, capsulitis, epicondylitis, tendinitis, panniculitis, osteochondritis / osteitis / osteomyelitis, spondylitis, periostitis, chondritis, nephritis, glomerulonephritis, pyelonephritis, ureteritis, cystitis, urethritis, oophoritis, salpingitis, endometritis, parametritis, cervicitis, vaginitis, vulvitis, mastitis, orchitis, epididymitis, prostatitis, seminalvesiculitis, balanitis, posthitis, balanoposthitis, chorioamnionitis, funisitis, omphalitis, insulitis, hypophysitis, thyroiditis, parathyroiditis, adrenalitis, lymphangitis, and lymphadenitis.Articles of Manufacture and KitsAlso provided are articles of manufacture comprising any of the compounds or pharmaceutical compositions described herein. The articles of manufacture include suitable containers or packaging materials for the compounds or pharmaceutical compositions. Examples of a suitable container include, but are not limited to, a bottle, a vial, a syringe, an intravenous bag, or a tube. Also provided are kits comprising any of the compounds or pharmaceutical compositions described herein. The kits can contain the compounds or pharmaceutical compositions in suitable containers or packaging materials, including, but not limited to, a bottle, a vial, a syringe, an intravenous bag, or a tube. The kits can comprise the compounds or pharmaceutical compositions for administration to a subject, cell, tissue, and / or individual in single-dose form or in multiple-dose form. The kits can further comprise instructions or a label for administering the compounds or pharmaceutical compositions to a subject, cell, tissue, and / or individual according to any of the methods disclosed herein. The kits can further comprise equipment for administering the compounds or pharmaceutical compositions to a subject, cell, tissue, and / or individual, including, but not limited to, needles, syringes, tubing, or intravenous bags. The kits can further comprise instructions for producing any of the compounds or pharmaceutical compositions disclosed herein. Also provided are articles of manufacture comprising any of the compounds or pharmaceutical compositions described herein. The articles of manufacture include suitable containers or packaging materials for the compounds or pharmaceutical compositions. The articles of manufacture include suitable containers or packaging materials for the compounds or pharmaceutical compositions. Examples of a suitable container include, but are not limited to, a bottle, a vial, a syringe, an intravenous bag, or a tube. This disclosure will be more fully understood by reference to the following Examples. They should not, however, be construed as limiting the scope of this disclosure. It is understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application and scope of the appended claims. EXAMPLES Additional embodiments are disclosed in further detail in the following examples, which are not in any way intended to limit the scope of the claims. Analytical Methods and Instrumentation Proton nuclear magnetic resonance (NMR) spectra were obtained on Bruker AscendTM500 MHz spectrometer. NMR spectra are reported as follows: chemical shift δ (ppm), multiplicity, coupling constant J (Hz), and (relative) integration. The abbreviations s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, and br = broad are used throughout. Mass spectral data were measured using the following systems: Waters Acquity i-class ultra-performance liquid chromatography (UPLC) system with Acquity Photo Diode Array Detector, Acquity Evaporative Light Scattering Detector (ELSD), and Waters ZQ Mass Spectrometer. Data was acquired using Waters MassLynx 4.1 software and purity was characterized by UV wavelength 220 nm, evaporative light scattering detection (ELSD), and electrospray positive ion (ESI) (column: Acquity UPLC BEH C181.7 µ ι 2.1 x 50 mm). Solvents used: acetonitrile / water, containing 0.1% formic acid; flow rate 0.7 mL / min. Preparatory HPLC purifications were conducted with a flow rate of 15 mL / min and detection by UV wavelength at 214 nm and 254 nm (Column: Jupiter© 10 µM Proteo 90 Å, 250 x 21.2 mm A, solvent: acetonitrile / water, containing a modifier such as 0.1% trifluoroacetic acid).

[0015] Abbreviations used in the examples include: Abbreviation Name CH3CN or acetonitrile ACN aq. aqueous atm atmospheres BINAP (1,1′-binaphthalene-2,2′-diyl)bis(diphenylphosphine) Boc t-butoxycarbonyl CCl4carbon tetrachloride CDCl3 deuterated chloroform CO carbon monoxide gas CO2carbon dioxide Cs2CO3 cesium carbonate CuBr copper(I) bromide Cu(OAc)2copper(II) acetate DCM dichloromethane DEAD diethyl azodicarboxylate DIPEA or diisopropylethylamine DIEA DMF N,N-dimethylformamide DMSO dimethylsulfoxide equiv equivalent ESI electrospray ionization Et3N triethylamine EtOAc ethyl acetate EtOH ethanol FA formic acid FC flash chromatography h or hr or hrs hours H2O water HATU 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3- oxide hexafluorophosphate HCl hydrogen chloride HOAc acetic acid K2CO3potassium carbonate KI potassium iodide KOH potassium hydroxide KOtBu potassium tert-butoxide LiAlH4lithium aluminum hydride LiOH lithium hydroxide MeOH methanol min minutes N2 nitrogen Na2CO3 sodium carbonate Abbreviation Name Na2SO4sodium sulfate NaH sodium hydride NaHCO3 sodium bicarbonate NaOH sodium hydroxide NBS N-bromosuccinimide NH4Cl ammonium chloride NMR nuclear magnetic resonance Pd2(dba)3tris(dibenzylideneacetone)dipalladium(0) Pd(dppf)Cl2 [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) Pd / C palladium on carbon Pd(OAc)2palladium(II) acetate PyBOP benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate Prep-TLC preparatory thin layer chromatography RuPhos-Pd-G2 chloro(2-dicyclohexylphosphino-2′,6′-diisopropoxy-1,1′-biphenyl)[2-(2′- amino-1,1′-biphenyl)]palladium(II) sat. saturated STAB sodium triacetoxyborohydride t-BuOH tert-butanol THF tetrahydrofuran T3P propylphosphonic anhydride

[0016] Docket No.: 121843.00294 NU-3600 PCT Table 1. Compounds Compound CHEMICAL STRUCTURE AND NAME Number MERICAS Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number N-(2-((2H-tetrazol-5-yl)amino)-2-oxoethyl)-2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H- [4,6'-biindazol]-1-yl)acetamide indazol]- Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number

[0017] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number 4-(4-(1-(2-((2-((carboxymethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid 162 4-(4-(5'-fluoro-1-(2-((2-((2-methoxy-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-1'-methyl- 1H,1'H-[4,6'-biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid 163 4-(4-(1-(2-((2-((2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-5'-fluoro-1'-methyl- 1H,1'H-[4,6'-biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid 164 - 207 - 1103012070\6\AMERICAS

[0018] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine 165 methyl (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate 166 tert-butyl (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate 167 - 208 - 1103012070\6\AMERICAS

[0019] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number (2-(5'-fluoro-1'-methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine 168 methyl (2-(5'-fluoro-1'-methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate 169 tert-butyl (2-(5'-fluoro-1'-methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate 170 - 209 - 1103012070\6\AMERICAS

[0020] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number 4-(4-(1-(2-((2-((carboxymethyl)amino)-2-oxoethyl)(methyl)amino)-2-oxoethyl)-5'-fluoro-1'-methyl- 1H,1'H-[4,6'-biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid 171 4-(4-(5'-fluoro-1-(2-((2-((2-methoxy-2-oxoethyl)amino)-2-oxoethyl)(methyl)amino)-2-oxoethyl)-1'- methyl-1H,1'H-[4,6'-biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid 172 4-(4-(1-(2-((2-((2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)(methyl)amino)-2-oxoethyl)-5'-fluoro-1'- methyl-1H,1'H-[4,6'-biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid 173 - 210 - 1103012070\6\AMERICAS

[0021] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number N-(2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)-N-methylglycylglycine 174 methyl N-(2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)-N-methylglycylglycinate 175 tert-butyl N-(2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]- 1-yl)acetyl)-N-methylglycylglycinate 176 - 211 - 1103012070\6\AMERICAS

[0022] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number N-(2-(5'-fluoro-1'-methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N- methylglycylglycine 177 methyl N-(2-(5'-fluoro-1'-methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)-N-methylglycylglycinate 178 tert-butyl N-(2-(5'-fluoro-1'-methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)-N-methylglycylglycinate - 212 - 1103012070\6\AMERICAS

[0023] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number 179 4-(4-(1-(2-((2-((carboxymethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-1'-methyl-1H,1'H-[4,6'-biindazol]- 3-yl)piperidin-1-yl)-4-oxobutanoic acid 180 4-(4-(1-(2-((2-((2-methoxy-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-1'-methyl-1H,1'H-[4,6'- biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid - 213 - 1103012070\6\AMERICAS

[0024] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number 181 4-(4-(1-(2-((2-((2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-1'-methyl-1H,1'H- [4,6'-biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid 182 (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine - 214 - 1103012070\6\AMERICAS

[0025] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number 183 methyl (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate 184 tert-butyl (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate - 215 - 1103012070\6\AMERICAS

[0026] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number 185 (2-(1'-methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine 186 methyl (2-(1'-methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate - 216 - 1103012070\6\AMERICAS

[0027] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number 187 tert-butyl (2-(1'-methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate 188 4-(4-(1-(2-((2-((carboxymethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-4-(5-fluoro-1-methyl-1H-indazol- 6-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)piperidin-1-yl)-4-oxobutanoic acid 189 - 217 - 1103012070\6\AMERICAS

[0028] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number 4-(4-(4-(5-fluoro-1-methyl-1H-indazol-6-yl)-1-(2-((2-((2-methoxy-2-oxoethyl)amino)-2-oxoethyl)amino)- 2-oxoethyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)piperidin-1-yl)-4-oxobutanoic acid 190 4-(4-(1-(2-((2-((2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-4-(5-fluoro-1-methyl- 1H-indazol-6-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)piperidin-1-yl)-4-oxobutanoic acid 191 (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-4-(5-fluoro-1-methyl-1H-indazol-6-yl)-1H-pyrazolo[3,4- b]pyridin-1-yl)acetyl)glycylglycine 192 - 218 - 1103012070\6\AMERICAS

[0029] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number methyl (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-4-(5-fluoro-1-methyl-1H-indazol-6-yl)-1H- pyrazolo[3,4-b]pyridin-1-yl)acetyl)glycylglycinate 193 tert-butyl (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-4-(5-fluoro-1-methyl-1H-indazol-6-yl)-1H- pyrazolo[3,4-b]pyridin-1-yl)acetyl)glycylglycinate 194 (2-(4-(5-fluoro-1-methyl-1H-indazol-6-yl)-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H-pyrazolo[3,4- b]pyridin-1-yl)acetyl)glycylglycine 195 - 219 - 1103012070\6\AMERICAS

[0030] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number methyl (2-(4-(5-fluoro-1-methyl-1H-indazol-6-yl)-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H-pyrazolo[3,4- b]pyridin-1-yl)acetyl)glycylglycinate 196 tert-butyl (2-(4-(5-fluoro-1-methyl-1H-indazol-6-yl)-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H- pyrazolo[3,4-b]pyridin-1-yl)acetyl)glycylglycinate 197 4-(4-(1-(2-((2-((carboxymethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-7'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid - 220 - 1103012070\6\AMERICAS

[0031] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number 198 4-(4-(7'-fluoro-1-(2-((2-((2-methoxy-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-1'-methyl- 1H,1'H-[4,6'-biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid 199 4-(4-(1-(2-((2-((2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-7'-fluoro-1'-methyl- 1H,1'H-[4,6'-biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid - 221 - 1103012070\6\AMERICAS

[0032] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number 200 (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-7'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine 201 methyl (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-7'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate - 222 - 1103012070\6\AMERICAS

[0033] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number 202 tert-butyl (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-7'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate 203 (2-(7'-fluoro-1'-methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine - 223 - 1103012070\6\AMERICAS

[0034] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number 204 methyl (2-(7'-fluoro-1'-methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate 205 tert-butyl (2-(7'-fluoro-1'-methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate - 224 - 1103012070\6\AMERICAS

[0035] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number 206 4-(4-(1-(2-((2-((carboxymethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-5'-fluoro-1H,1'H-[4,6'-biindazole]- 1'-carbonyl)piperidin-1-yl)-4-oxobutanoic acid 207 4-(4-(5'-fluoro-1-(2-((2-((2-methoxy-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-1H,1'H-[4,6'- biindazole]-1'-carbonyl)piperidin-1-yl)-4-oxobutanoic acid 208 4-(4-(1-(2-((2-((2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-5'-fluoro-1H,1'H-[4,6'- biindazole]-1'-carbonyl)piperidin-1-yl)-4-oxobutanoic acid - 225 - 1103012070\6\AMERICAS

[0036] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number 209 (2-(1'-(1-(4-amino-4-oxobutanoyl)piperidine-4-carbonyl)-5'-fluoro-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine 210 methyl (2-(1'-(1-(4-amino-4-oxobutanoyl)piperidine-4-carbonyl)-5'-fluoro-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate 211 tert-butyl (2-(1'-(1-(4-amino-4-oxobutanoyl)piperidine-4-carbonyl)-5'-fluoro-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate - 226 - 1103012070\6\AMERICAS

[0037] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number 212 (2-(5'-fluoro-1'-(1-(4-oxopentanoyl)piperidine-4-carbonyl)-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine 213 methyl (2-(5'-fluoro-1'-(1-(4-oxopentanoyl)piperidine-4-carbonyl)-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate 214 tert-butyl (2-(5'-fluoro-1'-(1-(4-oxopentanoyl)piperidine-4-carbonyl)-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate - 227 - 1103012070\6\AMERICAS

[0038] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number 215 methyl (2-(5'-fluoro-1'-methyl-3-(piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate 216 tert-butyl (2-(5'-fluoro-1'-methyl-3-(piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate - 228 - 1103012070\6\AMERICAS

[0039] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number 217 methyl (2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate 218 (2-(3-(1-acetylpiperidin-4-yl)-5',7'-difluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine - 229 - 1103012070\6\AMERICAS

[0040] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number 219 (2-(8-(5-fluoro-1-methyl-1H-indazol-6-yl)quinolin-4-yl)acetyl)glycylglycine 220 3-((2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)methyl)-4- fluorobenzoic acid 221 2-(2-((2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetamido)methyl)thiazol-4-yl)acetic acid - 230 - 1103012070\6\AMERICAS

[0041] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number 222 2-(4-((2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)methyl)- 1H-1,2,3-triazol-1-yl)acetic acid 223 (2-(3-(1-acetylpiperidin-4-yl)-7-amino-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine 224 (2-(5'-fluoro-1'-methyl-7-(methylthio)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine - 231 - 1103012070\6\AMERICAS

[0042] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number 225 N-(2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N- cyclopropylglycylglycine 226 2-(4-((2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N- methylacetamido)methyl)-1H-1,2,3-triazol-1-yl)acetic acid - 232 - 1103012070\6\AMERICAS

[0043] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number 227 N-(2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-2'-methyl-1H,2'H-[4,6'-biindazol]-1-yl)acetyl)-N- cyclopropylglycylglycine 228 N-(2-(3-(2-acetyl-2-azaspiro[3.3]heptan-6-yl)-5'-cyano-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N- methylglycylglycine - 233 - 1103012070\6\AMERICAS

[0044] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number 229 methyl (2-(5'-fluoro-1'-methyl-3-(1-(4-(methylamino)-4-oxobutanoyl)piperidin-4-yl)-1H,1'H-[4,6'- biindazol]-1-yl)acetyl)glycylglycinate 230 (2-(3-(1-acetylpiperidin-4-yl)-4-(isoquinolin-3-yl)-1H-indazol-1-yl)acetyl)glycylglycine 231 (2-(3-(1-acetylpiperidin-4-yl)-4-(1-methyl-1H-indol-6-yl)-1H-indazol-1-yl)acetyl)glycylglycine - 234 - 1103012070\6\AMERICAS

[0045] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number 232 (2-(3-(1-(20-chloro-4-oxo-8,11,14-trioxa-5-azaicosanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)acetyl)glycylglycine 233 methyl (2-(3-(1-(20-chloro-4-oxo-8,11,14-trioxa-5-azaicosanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl- 1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate 234 (2-(3-(1-(23-chloro-4-oxo-8,11,14,17-tetraoxa-5-azatricosanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl- 1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine - 235 - 1103012070\6\AMERICAS

[0046] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number 235 methyl (2-(3-(1-(23-chloro-4-oxo-8,11,14,17-tetraoxa-5-azatricosanoyl)piperidin-4-yl)-5'-fluoro-1'- methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate 236 (2-(3-(1-(26-chloro-4-oxo-8,11,14,17,20-pentaoxa-5-azahexacosanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl- 1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine 237 methyl (2-(3-(1-(26-chloro-4-oxo-8,11,14,17,20-pentaoxa-5-azahexacosanoyl)piperidin-4-yl)-5'-fluoro-1'- methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate - 236 - 1103012070\6\AMERICAS

[0047] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number 238 (2-(3-(1-(29-chloro-4-oxo-8,11,14,17,20,23-hexaoxa-5-azanonacosanoyl)piperidin-4-yl)-5'-fluoro-1'- methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine 239 methyl (2-(3-(1-(29-chloro-4-oxo-8,11,14,17,20,23-hexaoxa-5-azanonacosanoyl)piperidin-4-yl)-5'-fluoro- 1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate 240 (S)-5-(2-fluoro-6-hydroxypyridin-3-yl)-N-methyl-2-((1-(3-((1-methyl-1H-tetrazol-5- yl)methoxy)benzoyl)piperidin-3-yl)methoxy)benzamide - 237 - 1103012070\6\AMERICAS

[0048] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number 241 (R)-5-(2-fluoro-6-hydroxypyridin-3-yl)-N-methyl-2-((1-(3-((1-methyl-1H-tetrazol-5- yl)methoxy)benzoyl)piperidin-3-yl)methoxy)benzamide 242 (S)-5-(2-fluoro-6-hydroxypyridin-3-yl)-N-methyl-2-((4-(3-((1-methyl-1H-tetrazol-5- yl)methoxy)benzoyl)morpholin-2-yl)methoxy)benzamide 243 (R)-5-(2-fluoro-6-hydroxypyridin-3-yl)-N-methyl-2-((4-(3-((1-methyl-1H-tetrazol-5- yl)methoxy)benzoyl)morpholin-2-yl)methoxy)benzamide 244 - 238 - 1103012070\6\AMERICAS

[0049] Docket No.: 121843.00294 NU-3600 PCT Compound CHEMICAL STRUCTURE AND NAME Number N-(2-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)ethyl)-6-(4-(2-(1-(2-(3,5- dioxomorpholino)acetamido)cyclobutyl)acetamido)piperidin-1-yl)nicotinamide 245 N-(2-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)ethyl)-5-((2-(3,5-dioxomorpholino)-N-(imidazo[2,1-b]thiazol- 3-ylmethyl)acetamido)methyl)-2,4-dimethylbenzamide - 239 - 1103012070\6\AMERICAS

[0050] Synthesis of Common Intermediate tert-butyl 4-(4-bromo-1-(2-ethoxy-2- oxoethyl)-1H-indazol-3-yl)piperidine-1-carboxylate (5) Step-1: Synthesis of tert-butyl 4-((2-bromo-6- fluorophenyl)(hydroxy)methyl)piperidine-1-carboxylate (2) To a stirred solution of 1-bromo-3-fluoro-2-iodobenzene (14 g, 80.460 mmol, 1 equiv) in THF (150 mL) was added dropwise LDA (2 M, 44 mL, 88.0 mmol, 1.1 equiv) at -78 °C under a nitrogen atmosphere. The resulting mixture was stirred at -78 °C under the nitrogen atmosphere for one hour. Then tert-butyl 4-formylpiperidine-1-carboxylate (34.32 g, 160.920 mmol, 2 equiv) in THF (50 mL) was added to the above mixture. The resulting mixture was stirred at -78 °C under the nitrogen atmosphere for one hour. The mixture was quenched with water. The resulting solution was concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with petroleum ether (PE):EtOAc = 1:1 to afford tert-butyl 4-((2- bromo-6-fluorophenyl)(hydroxy)methyl)piperidine-1-carboxylate (25.86 g, 82.78% yield, 90.0% purity) as a yellow oil. m / z = 388.1 (M+H)+. Step-2: Synthesis of tert-butyl 4-(2-bromo-6-fluorobenzoyl)piperidine-1- carboxylate (3) To a stirred solution of tert-butyl 4-((2-bromo-6- fluorophenyl)(hydroxy)methyl)piperidine-1-carboxylate (25 g, 64.387 mmol, 90.0% purity, 1 equiv) in DCM (100 mL) was added PCC (27.76 g, 128.774 mmol, 2 equiv). The resulting mixture was stirred at room temperature overnight. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE:EtOAc = 3:1 to afford tert-butyl 4-(2-bromo-6-fluorobenzoyl)piperidine-1-carboxylate (18.85 g, 75.79% yield, 85.0% purity) as a yellow solid. m / z = 386.1 (M+H)+. Step-3: Synthesis of tert-butyl 4-(4-bromo-1H-indazol-3-yl)piperidine-1- carboxylate (4) To a stirred solution of tert-butyl 4-(2-bromo-6-fluorobenzoyl)piperidine-1- carboxylate (16.85 g, 43.623 mmol, 85.0% purity, 1 equiv) in dioxane (50 mL) was added N2H4·H2O (10.92 g, 218.115 mmol, 5 equiv). The resulting mixture was stirred at 110 °C for 2 hr. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with PE:EtOAc = 1:1 to afford tert-butyl 4-(4-bromo-1H- indazol-3-yl)piperidine-1-carboxylate (11 g, 66.31% yield, 88.0% purity) as a yellow solid. m / z = 380.1 (M+H)+. Step-4: Synthesis of tert-butyl 4-(4-bromo-1-(2-ethoxy-2-oxoethyl)-1H-indazol-3- yl)piperidine-1-carboxylate (5) To a stirred solution of tert-butyl 4-(4-bromo-1H-indazol-3-yl)piperidine-1- carboxylate (1 g, 2.630 mmol, 88.0% purity, 1 equiv) in DMF (10 mL) was added K2CO3(0.73 g, 5.260 mmol, 2 equiv) and ethyl bromoacetate (0.44 g, 2.630 mmol, 1 equiv). The resulting mixture was stirred at 80 °C under a nitrogen atmosphere for 4 hr. The resulting solution was diluted with water and extracted with ethyl acetate. The organic layers were combined and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with PE:EtOAc = 2:1 to afford tert-butyl 4-(4-bromo-1-(2-ethoxy-2-oxoethyl)-1H-indazol-3- yl)piperidine-1-carboxylate (800 mg, 65.57% yield, 90.0% purity) as a white solid. m / z = 466.1 (M+H)+. Synthesis of Commonly Employed Boronic Acid Pinacol Ester (3).

[0051] Step-1: Synthesis of 6-bromo-5-fluoro-1-methylindazole (2) To a stirred solution of 6-bromo-5-fluoro-1H-indazole (10 g, 46.506 mmol, 1 equiv) in MeCN (30 mL) was added Cs2CO3(30.31 g, 93.012 mmol, 2 equiv) and MeI (7.92 g, 55.807 mmol, 1.2 equiv). The resulting mixture was stirred at 70 °C for 3 h under a nitrogen atmosphere. The resulting mixture was then concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with petroleum ether:ethyl acetate = 2:1 to afford 6-bromo-5-fluoro-1-methylindazole (8 g, 75.10% yield, 90.0% purity) as a light yellow solid. m / z = 229.0 (M+H)+. Step-2: Synthesis of 5-fluoro-1-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan- 2-yl)indazole (3) To a stirred solution of 6-bromo-5-fluoro-1-methylindazole (4.1 g, 17.900 mmol, 90% purity, 1.0 equiv) in 1,4-dioxane (100 mL) was added Pd(dppf)Cl2 (2.62 g, 3.580 mmol, 0.2 equiv), bis(pinacolato)diboron (11.36 g, 44.750 mmol, 2.5 equiv), and KOAc (8.78 g, 89.500 mmol, 5 equiv). The resulting mixture was stirred at 90 °C for 2 h under a nitrogen atmosphere. The mixture was then concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with petroleum ether:ethyl acetate = 3:1 to afford 5-fluoro-1-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) indazole (4.2176 g, 84.91% yield, 99.5% purity) as a light orange solid. LCMS: Rt = 1.478 min, m / z = 277.0 (M+H)+.1H NMR (300 MHz, DMSO-d6) δ 8.02 (d, J = 1.2 Hz, 1H), 7.90 – 7.85 (m, 1H), 7.47 (d, J = 9.6 Hz, 1H), 4.09 (s, 3H), 1.34 (s, 12H). General Pathway Towards Installing Substituents to Explore the SAR of Di- glycine.

[0052] Step-1: Synthesis of tert-butyl 4-[1-(2-ethoxy-2-oxoethyl)-5'-fluoro-1'-methyl- [4,6'-biindazol]-3-yl]piperidine-1-carboxylate (6) To a stirred solution of tert-butyl 4-[4-bromo-1-(2-ethoxy-2-oxoethyl)indazol-3- yl]piperidine-1-carboxylate (300 mg, 0.643 mmol, 90.0% purity, 1 equiv) in dioxane (5 mL):H2O (1 mL) was added K2CO3 (240.03 g, 1.736 mmol, 2 equiv), 5-fluoro-1-methyl-6-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)indazole (335.6 mg, 1.215 mmol, 1.89 equiv) and Pd(dppf)Cl2·CH2Cl2(57.6 mg, 0.071 mmol, 0.10 equiv). The resulting mixture was stirred at 75 °C under a nitrogen atmosphere for 2 h. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with PE:EtOAc = 5:1 to afford tert-butyl 4-[1-(2-ethoxy-2-oxoethyl)-5'-fluoro-1'-methyl-[4,6'-biindazol]-3- yl]piperidine-1-carboxylate (370 mg, 93.19% yield, 90.0% purity) as a light yellow solid. m / z = 536.2 (M+H)+. Step-2: Synthesis of ethyl 2-[5'-fluoro-1'-methyl-3-(piperidin-4-yl)-[4,6'- biindazol]-1-yl]acetate (7) To a stirred solution of tert-butyl 4-[1-(2-ethoxy-2-oxoethyl)-5'-fluoro-1'-methyl- [4,6'-biindazol]-3-yl] piperidine-1-carboxylate (370 mg, 0.691 mmol, 90.0% purity, 1 equiv) in DCM (5 mL) was added HCl (gas) in 1,4-dioxane (4 M, 5 mL). The resulting mixture was stirred at room temperature for 2 h. The resulting mixture was concentrated under reduced pressure to afford ethyl 2-[5'-fluoro-1'-methyl-3-(piperidin-4-yl)-[4,6'-biindazol]-1-yl]acetate (250 mg, 83.00% yield, 90.0% purity) as a light yellow solid. m / z = 436.2 (M+H)+. Step-3: Synthesis of ethyl 2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'- biindazol]-1-yl]acetate (8) To a stirred solution of ethyl 2-[5'-fluoro-1'-methyl-3-(piperidin-4-yl)-[4,6'- biindazol]-1-yl]acetate (250 mg, 0.620 mmol, 90.0% purity, 1 equiv) in DCM (5 mL) was added TEA (186.9 mg, 1.848 mmol, 2.98 equiv) and acetyl chloride (72.3 mg, 0.918 mmol, 1.48 equiv). The resulting mixture was stirred at room temperature under nitrogen atmosphere for 1.5 h. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with PE:EtOAc = 5:1 to afford ethyl 2-[3-(1-acetylpiperidin-4-yl)- 5'-fluoro-1'-methyl-[4,6'-biindazol]-1-yl]acetate (280 mg, 91.33% yield, 88.0% purity) as a light yellow solid. m / z = 478.2 (M+H)+. Step-4: Synthesis of [3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'- biindazol]-1-yl]acetic acid (9) To a stirred solution of ethyl 2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl- [4,6'-biindazol]-1-yl]acetate (255 mg, 0.534 mmol, 88.0% purity, 1 equiv) in THF (2 mL):H2O (2 mL):MeOH (2 mL) was added LiOH·H2O (63.8 mg, 1.522 mmol, 2.85 equiv). The resulting mixture was stirred at room temperature overnight. The resulting mixture was concentrated under reduced pressure. The residue was acidified to pH 5 with HCl (aq.1 M). The precipitated solids were collected by filtration, washed with water, dried, and the volatiles were removed under reduced pressure to afford [3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'-biindazol]-1- yl]acetic acid (120 mg, 50.00% yield, 90.0% purity) as a light yellow solid. m / z = 450.2 (M+H)+. Step-5: Synthesis of methyl 2-{2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl- [4,6'-biindazol]-1-yl]-N-methylacetamido}acetate (10) To a stirred solution of [3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'- biindazol]-1-yl]acetic acid (120 mg, 0.267 mmol, 90.0% purity, 1.00 equiv) in DMF (5 mL) was added methyl 2-(methylamino)acetate hydrochloride (37.1 mg, 0.267 mmol, 1 equiv), HATU (152.2 mg, 0.401 mmol, 1.5 equiv), and DIEA (172.5 mg, 1.335 mmol, 5 equiv). The resulting mixture was stirred at room temperature for 1.5 h. The resulting solution was diluted with water and extracted with ethyl acetate. The organic layers were combined and concentrated under reduced pressure. The residue was purified by reverse phase column chromatography with acetonitrile (ACN):H2O (1:3) to afford methyl 2-{2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'- methyl-[4,6'-biindazol]-1-yl]-N-methylacetamido}acetate (140 mg, 95.10% yield, 85.0% purity) as a white solid. m / z = 535.2 (M+H)+. Step-6: Synthesis of {2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'- biindazol]-1-yl]-N-methylacetamido}acetic acid (11) To a stirred solution of methyl 2-{2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'- methyl-[4,6'-biindazol]-1-yl]-N-methylacetamido}acetate (150 mg, 0.281 mmol, 85.0% purity, 1 equiv) in THF (2 mL):H2O (2 mL):MeOH (2 mL) was added LiOH·H2O (13.4 mg, 0.562 mmol, 2 equiv). The resulting mixture was stirred at room temperature for 2 h. The resulting mixture was concentrated under reduced pressure. The residue was acidified to pH 5 with HCl (aq.1 M). The precipitated solids were collected by filtration, washed with water, dried, and the volatiles were removed under reduced pressure to afford {2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'- biindazol]-1-yl]-N-methylacetamido}acetic acid (100 mg, 68.46%, 92.0% purity) as a white solid. m / z = 521.2 (M+H)+Step-7: Synthesis of ethyl 2-(2-{2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl- [4,6'-biindazol]-1-yl]-N-methylacetamido}acetamido)acetate (12) To a stirred solution of {2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'- biindazol]-1-yl]-N-methylacetamido}acetic acid (100 mg, 0.192 mmol, 92.0% purity, 1 equiv) in ACN (5 mL) was added NMI (157.7 mg, 1.920 mmol, 10 equiv), glycine ethyl ester hydrochloride (40 mg, 0.288 mmol, 1.5 equiv), and TCFH (80.8 mg, 0.288 mmol, 1.5 equiv). The resulting mixture was stirred at room temperature for one hour. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with PE:EtOAc = 1:1 to afford ethyl 2-(2-{2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'- biindazol]-1-yl]-N-methylacetamido}acetamido)acetate (80 mg, 68.76% yield, 90.0% purity) as a yellow solid. m / z = 606.3 (M+H)+. Step-8: Synthesis of (2-{2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'- biindazol]-1-yl]-N-methylacetamido}acetamido)acetic acid (13) To a stirred solution of ethyl 2-(2-{2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'- methyl-[4,6'-biindazol]-1-yl]-N-methylacetamido}acetamido)acetate (60 mg, 0.099 mmol, 90.0% purity, 1 equiv) in THF (1 mL):H2O (1 mL):MeOH (1 mL) was added LiOH·H2O (4.7 mg, 0.198 mmol, 2 equiv). The resulting mixture was stirred at room temperature for 2 h. The resulting mixture was concentrated under reduced pressure. The residue was acidified to pH 5 with HCl (aq. 1 M). The resulting solution was concentrated under reduced pressure. The residue was purified by reverse phase column chromatography with ACN:H2O (1:3) to afford (2-{2-[3-(1- acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'-biindazol]-1-yl]-N- methylacetamido}acetamido)acetic acid (29.7 mg, 51.39% yield, 99.0% purity) as a white solid. LCMS: Rt = 1.504 min, m / z = 578.25 (M+H)+.1H NMR (400 MHz, Methanol-d4) δ 8.24 – 7.99 (m, 1H), 7.73 – 7.59 (m, 3H), 7.55 – 7.46 (m, 1H), 7.15 – 7.07 (m, 1H), 5.49 (d, J = 1.6 Hz, 1H), 5.41 (s, 1H), 4.43 (d, J = 6.4 Hz, 1H), 4.35 (s, 1H), 4.24 (d, J = 9.6 Hz, 1H), 4.17 (d, J = 1.6 Hz, 1H), 4.12 (s, 3H), 3.95 – 3.81 (m, 2H), 3.69 (d, J = 8.0 Hz, 1H), 3.29 (s, 1H), 3.01 (s, 1H), 2.74 – 2.60 (m, 1H), 2.49 – 2.15 (m, 1H), 2.01 (d, J = 8.4 Hz, 3H), 1.96 – 1.78 (m, 2H), 1.69 (d, J = 12.4 Hz, 1H), 1.63 – 1.41 (m, 2H). General Pathway to Install Substituents for Exploring the SAR of the Biaryl.

[0053] Step-1: Synthesis of ethyl 2-[4-bromo-3-(piperidin-4-yl)indazol-1-yl]acetate (2) To a stirred solution of tert-butyl 4-[4-bromo-1-(2-ethoxy-2-oxoethyl)indazol-3- yl]piperidine-1-carboxylate (6.5 g, 13.978 mmol, 1 equiv) was added HCl (gas) in 1,4-dioxane (15 mL). The resulting mixture was stirred at room temperature for 2 h. The resulting mixture was concentrated under reduced pressure to afford ethyl 2-[4-bromo-3-(piperidin-4-yl)indazol-1- yl]acetate (5 g, 88.20% yield, 90.0% purity) as a yellow solid. m / z = 366.2 (M+H)+. Step-2: Synthesis of ethyl 2-[3-(1-acetylpiperidin-4-yl)-4-bromoindazol-1- yl]acetate (3) To a stirred solution of ethyl 2-[4-bromo-3-(piperidin-4-yl)indazol-1-yl]acetate (5 g, 13.652 mmol, 90% purity, 1.0 equiv) in DCM (15 mL) was added acetyl chloride (1.29 g, 16.382 mmol, 1.2 equiv) and TEA (4.14 g, 40.956 mmol, 3 equiv). The resulting mixture was stirred at room temperature under a nitrogen atmosphere for 2 h. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with petroleum ether:ethyl acetate = 3:1 to afford ethyl 2-[3-(1- acetylpiperidin-4-yl)-4-bromoindazol-1-yl]acetate (5 g, 89.70% yield, 90.0% purity) as a yellow solid. m / z = 408.2 (M+H)+. Step-3: Synthesis of [3-(1-acetylpiperidin-4-yl)-4-bromoindazol-1-yl]acetic acid (4) To a stirred solution of ethyl 2-[3-(1-acetylpiperidin-4-yl)-4-bromoindazol-1- yl]acetate (5 g, 12.246 mmol, 90% purity, 1.0 equiv) in THF (10 mL):H2O (10 mL):MeOH (10 mL) was added LiOH (0.59 g, 24.492 mmol, 2 equiv). The resulting mixture was stirred at room temperature for 2 h. The solution was then concentrated under reduced pressure and acidified to pH 4 with HCl (1 M). The mixture was then extracted with EtOAc. The organic layers were combined and evaporated to afford [3-(1-acetylpiperidin-4-yl)-4-bromoindazol-1-yl]acetic acid (4 g, 85.90% yield, 90.0% purity) as a white solid. m / z = 380.2 (M+H)+. Step-4: Synthesis of methyl 2-(2-{2-[3-(1-acetylpiperidin-4-yl)-4-bromoindazol-1- yl]acetamido}acetamido)acetate (5) To a stirred solution of [3-(1-acetylpiperidin-4-yl)-4-bromoindazol-1-yl]acetic acid (4 g, 10.520 mmol, 90% purity, 1.0 equiv) in ACN (20 mL) was added NMI (8.64 g, 105.200 mmol, 10 equiv), TCFH (4.43 g, 15.780 mmol, 1.5 equiv), and methyl 2-(2- aminoacetamido)acetate hydrochloride (2.31 g, 12.624 mmol, 1.2 equiv). The resulting mixture was stirred at room temperature for 2 h. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with petroleum ether:ethyl acetate = 1:1 to afford methyl 2-(2-{2-[3-(1-acetylpiperidin-4-yl)-4-bromoindazol-1- yl]acetamido}acetamido)acetate (4 g, 74.80% yield, 90.0% purity) as a white solid. m / z = 507.1 (M+H)+. Step-5: Synthesis of (2-{2-[3-(1-acetylpiperidin-4-yl)-1'-methyl-[4,6'-biindazol]- 1-yl]acetamido}acetamido)acetic acid (6) To a stirred solution of methyl 2-(2-{2-[3-(1-acetylpiperidin-4-yl)-4- bromoindazol-1-yl]acetamido}acetamido)acetate (100 mg, 0.197 mmol, 90% purity, 1.0 equiv) in dioxane (10 mL):H2O (2 mL) was added 1-methylindazol-6-ylboronic acid (34.62 mg, 0.197 mmol, 1 equiv), K2CO3(54.37 mg, 0.394 mmol, 2 equiv), and Pd(dppf)Cl2(28.79 mg, 0.039 mmol, 0.2 equiv). The resulting mixture was stirred at 75 °C under a nitrogen atmosphere for 2 h. The resulting mixture was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18; mobile phase, acetonitrile in water (NH4HCO3), 20% to 25% gradient in 10 min; and detector, UV 254 nm, to afford (2-{2-[3-(1-acetylpiperidin-4-yl)-1'-methyl-[4,6'-biindazol]-1- yl]acetamido}acetamido)acetic acid (10.5 mg, 9.76% yield, 99.8% purity) as a white solid. LCMS: Rt = 1.268 min, m / z = 546.2 (M+H)+.1H NMR (300 MHz, Methanol-d4) δ 8.13 (s, 1H), 7.89 (d, J = 8.4 Hz, 1H), 7.67 (s, 1H), 7.59 (d, J = 8.4 Hz, 1H), 7.54 – 7.44 (m, 1H), 7.37 – 7.24 (m, 1H), 7.15 (d, J = 6.9 Hz, 1H), 5.21 (s, 2H), 4.42 – 4.21 (m, 1H), 4.13 (s, 3H), 3.96 (d, J = 8.7 Hz, 4H), 3.82 – 3.63 (m, 1H), 2.92 – 2.71 (m, 1H), 2.52 (s, 1H), 2.00 (s, 4H), 1.70 (s, 4H). Example 1 Synthesis of 2-{2-[2-(1H-indol-1-yl)acetamido]acetamido}acetic acid Step-1: Synthesis of indole-1-acetic acid Indole (1.54 g, 13.1454 mmol), potassium carbonate (4.54 g, 32.8636 mmol), and DMF (20 mL) were charged to a 100 mL round-bottomed flask. While stirring, ethyl bromoacetate (1.04 mL, 1.57 g, 9.3896 mmol) was added. A reflux condenser was fitted to the flask and the mixture stirred overnight at 70 °C. The mixture was then cooled to room temperature. LCMS showed incomplete conversion. The mixture was filtered and the filtrate was concentrated. The crude was dissolved in methanol (15 mL) and lithium hydroxide monohydrate (15.00 mL, 2.52 g, 60.0000 mmol) was added. LCMS showed the desired product. The pH was adjusted to 4 with saturated aqueous citric acid. The aqueous was extracted with ethyl acetate (3 x 20 mL). The organic phase was dried on sodium sulfate, filtered, and concentrated. The crude was chromatographed on a 24 g silica gel column (0-10% MeOH:DCM) yielding indole-1-acetic acid (0.432 g, 18.76%). LCMS m / z: 176.2. Step-2: Synthesis of (2-(1H-indol-1-yl)acetyl)glycylglycine Indole-1-acetic acid (20.00 mg, 0.1142 mmol), [(dimethylamino)({[1,2,3]triazolo[4,5-b]pyridin-3- yloxy})methylidene]dimethylazanium; hexafluoro-lambda5-phosphanuide (43.41 mg, 0.1142 mmol), and DMF (0.3 mL) were added to a 1-dram vial. N,N-diisopropylethylamine (79.76 µL, 59.02 mg, 0.4567 mmol) was added and the mixture was stirred at room temperature.150 µL of the mixture was submitted for HPLC purification of the intermediate methyl ester. The remaining mixture was treated with lithium hydroxide monohydrate (0.30 mL, 0.05 g, 1.2000 mmol) at room temperature. LCMS after stirring for one hour showed the desired product. The pH was adjusted to 4 with saturated aqueous citric acid. The crude was submitted for HPLC purification yielding (2-(1H-indol-1-yl)acetyl)glycylglycine (0.0042 g, 12.72%). LCMS for C14H15N3O4 required: 289.29, found m / z: 289.9 [M+H]+.1H NMR (500 MHz, DMSO-d6) δ 8.40 (t, J = 5.8 Hz, 1H), 8.22 (t, J = 5.8 Hz, 1H), 7.54 (dt, J = 7.9, 1.0 Hz, 1H), 7.39 (dt, J = 8.2, 0.9 Hz, 1H), 7.33 (d, J = 3.1 Hz, 1H), 7.11 (ddd, J = 8.2, 7.1, 1.2 Hz, 1H), 7.02 (ddd, J = 7.9, 7.0, 0.9 Hz, 1H), 6.43 (dd, J = 3.1, 0.9 Hz, 1H), 4.89 (s, 2H), 3.77 (dd, J = 13.5, 5.7 Hz, 4H). Example 2 Synthesis of 2-[2-(2-{5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl}acetamido)acetamido]acetic acid

[0054] Step-1: Synthesis of ethyl 2-(4-bromoindazol-1-yl) acetate (2) To a stirred solution of 4-bromo-1H-indazole (10 g, 50.752 mmol, 1.0 equiv) in DMF (30 mL) was added ethyl 2-bromoacetate (8.47 g, 50.752 mmol, 1.0 equiv) and K2CO3 (14.02 g, 101.504 mmol, 2 equiv). The resulting mixture was stirred at 80 °C overnight under a nitrogen atmosphere. The resulting mixture was diluted with water and extracted with ethyl acetate. The organic layer was concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with PE:EtOAc = 5:1 to afford ethyl 2-(4-bromoindazol-1-yl) acetate (8 g, 55.67% yield, 90.0% purity) as a white solid. m / z = 283.0 (M+H)+. Step-2: Synthesis of ethyl 2-{5'-fluoro-1'-methyl-[4,6'-biindazol]-1-yl}acetate (3) To a stirred solution of ethyl 2-(4-bromoindazol-1-yl) acetate (500 mg, 1.766 mmol, 90% purity, 1.0 equiv) in 1,4-dioxane (5 mL) and H2O (1 mL) was added 5-fluoro-1- methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indazole (731.4mg, 2.649 mmol, 1.5 equiv), Pd(dppf)Cl2 (143.8 mg, 0.177 mmol, 0.1 equiv), and K2CO3 (536.9 mg, 3.885 mmol, 2.0 equiv). The resulting mixture was stirred at 75 °C for 2 h under a nitrogen atmosphere. The resulting mixture was then concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with PE:EtOAc = 1:1 to afford ethyl 2-{5'-fluoro-1'-methyl- [4,6'-biindazol]-1-yl}acetate (380 mg, 61.07% yield, 90.0% purity) as a white solid. m / z = 353.1 (M+H)+. Step-3: Synthesis of {5'-fluoro-1'-methyl-[4,6'-biindazol]-1-yl}acetic acid (4) To a stirred solution of ethyl 2-{5'-fluoro-1'-methyl-[4,6'-biindazol]-1-yl}acetate (350 mg, 0.993 mmol, 90% purity, 1.0 equiv) in THF (3 mL):H2O (3 mL):MeOH (3 mL) was added LiOH (47.5 mg, 1.986 mmol, 2.0 equiv). The resulting mixture was stirred at room temperature for 2 h. The resulting mixture was then concentrated under reduced pressure. The residue was acidified to pH 5 with HCl (aq.1 M) and concentrated under vacuum. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18; mobile phase, ACN in Water (0.1% NH4HCO3), 30% to 40% gradient in 10 min; detector, UV 254 nm, to afford {5'-fluoro-1'-methyl-[4,6'-biindazol]-1-yl} acetic acid (260 mg, 80.71% yield, 90.0% purity) as a white solid. m / z = 325.1 (M+H)+. Step-4: Synthesis of methyl 2-[2-(2-{5'-fluoro-1'-methyl-[4,6'-biindazol]- 1yl}acetamido) acetamido]acetate (5) To a stirred solution of {5'-fluoro-1'-methyl-[4,6'-biindazol]-1-yl} acetic acid (140 mg, 0.432 mmol, 90% purity, 1.0 equiv) in DMF (5 mL) was added methyl 2-(2- aminoacetamido)acetate hydrochloride (78.6 mg, 0.432 mmol, 1.0 equiv), NMI (354.4 mg, 4.320 mmol, 10 equiv), and TCFH (181.6 mg, 0.648 mmol, 1.5 equiv). The resulting mixture was stirred at room temperature for 2 h under a nitrogen atmosphere. The resulting mixture was then diluted with water and extracted with ethyl acetate. The organic layer was concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with DCM:MeOH = 20:1 to afford methyl 2-[2-(2-{5'-fluoro-1'-methyl-[4,6'-biindazol]-1-yl} acetamido) acetamido] acetate (100 mg, 51.20% yield, 90.0% purity) as a white solid. m / z = 453.2 (M+H)+. Step-5: Synthesis of [2-(2-{5'-fluoro-1'-methyl-[4,6'-biindazol]-1-yl} acetamido) acetamido] acetic acid (6) To a stirred solution of methyl 2-[2-(2-{5'-fluoro-1'-methyl-[4,6'-biindazol]-1-yl} acetamido) acetamido] acetate (90 mg, 0.199 mmol, 90% purity, 1.0 equiv) in H2O (2 mL):THF (2 mL):MeOH (2 mL) was added LiOH (9.5 mg, 0.398 mmol, 2.0 equiv). The resulting solution was stirred at room temperature for 2 h. The resulting mixture was then concentrated under reduced pressure. The residue was acidified to pH 5 with HCl (aq.1 M) and concentrated under vacuum. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18; mobile phase, ACN in Water (0.1% NH4HCO3), 20% to 30% gradient in 10 min; detector, UV 254 nm. This resulted in [2-(2-{5'-fluoro-1'-methyl-[4,6'-biindazol]-1-yl} acetamido) acetamido] acetic acid (39.6 mg, 45.36% yield, 99.9% purity) as a white solid. LCMS for C21H19FN6O4 required: 438.42, found Rt = 1.094 min, m / z: 439.1 [M+H]+.1H NMR (400 MHz, Methanol-d4) δ 8.11 (s, 1H), 7.99 (s, 1H), 7.87 (d, J = 5.9 Hz, 1H), 7.77 – 7.69 (m, 1H), 7.56 – 7.47 (m, 2H), 7.29 (d, J = 7.0 Hz, 1H), 5.24 (s, 2H), 4.11 (s, 3H), 3.78 (d, J = 5.6 Hz, 2H), 3.48 (d, J = 4.9 Hz, 2H). Example 3 Synthesis of 2-(2-{2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl]acetamido}-N-methylacetamido)acetic acid

[0055] Step-1: Synthesis of methyl 2-(2-{2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'- methyl-[4,6'-biindazol]-1-yl]acetamido}-N-methylacetamido)acetate (2) To a stirred solution of {2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'- biindazol]-1-yl]acetamido}acetic acid (100 mg, 0.197 mmol, 1 equiv) in ACN (4 mL) was added NMI (162.1 mg, 1.970 mmol, 10 equiv), methyl 2-(methylamino)acetate hydrochloride (54.8 mg, 0.394 mmol, 2 equiv), and TCFH (110.8 mg, 0.394 mmol, 2 equiv). The resulting mixture was stirred at room temperature for 2 h. The resulting mixture was then concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with PE:EtOAc = 1:1 to afford methyl 2-(2-{2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'- biindazol]-1-yl]acetamido}-N-methylacetamido)acetate (80 mg, 42.81% yield, 90.0% purity) as a white solid. m / z = 592.3 (M+H)+. Step-2: Synthesis of (2-{2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'- biindazol]-1-yl]acetamido}-N-methylacetamido)acetic acid (3) To a stirred solution of methyl 2-(2-{2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'- methyl-[4,6'-biindazol]-1-yl]acetamido}-N-methylacetamido)acetate (80 mg, 0.135 mmol, 90.0% purity, 1 equiv) in THF (1 mL):H2O (1 mL):MeOH (1 mL) was added LiOH (6.5 mg, 0.270 mmol, 2 equiv). The resulting mixture was stirred at room temperature for 2 h. The resulting mixture was then concentrated under reduced pressure. The residue was acidified to pH 5 with HCl (aq. 1 M). The resulting mixture was concentrated under vacuum. The residue was purified by reverse phase column chromatography with ACN:H2O (1:3) to afford (2-{2-[3-(1-acetylpiperidin-4-yl)- 5'-fluoro-1'-methyl-[4,6'-biindazol]-1-yl]acetamido}-N-methylacetamido)acetic acid (22.8 mg, 28.84% yield, 98.8% purity) as a white solid. LCMS for C29H32FN7O5 required: 577.2, found Rt = 1.522 min, m / z: 578.2 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.28 – 8.05 (m, 2H), 7.89 – 7.79 (m, 1H), 7.77 – 7.61 (m, 2H), 7.53 – 7.39 (m, 1H), 7.10 (d, J = 6.4 Hz, 1H), 5.29 – 5.07 (m, 2H), 4.34 – 3.99 (m, 5H), 3.94 – 3.82 (m, 2H), 3.76 – 3.53 (m, 3H), 2.95 (s, 1H), 2.80 (s, 2H), 2.37 – 2.16 (m, 1H), 1.89 (d, J = 12.8 Hz, 3H), 1.79 – 1.59 (m, 2H), 1.55 – 1.41 (m, 2H), 1.34 – 1.20 (m, 1H). Example 4 Synthesis of 2-{2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl]acetamido}-N-(carbamoylmethyl)acetamide Step-1: Synthesis of ethyl 2-{2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl- [4,6'-biindazol]-1-yl]acetamido}acetate (2) To a stirred solution of [3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'- biindazol]-1-yl]acetic acid (200 mg, 0.445 mmol, 1 equiv) in ACN (5 mL) was added NMI (365.3 mg, 4.450 mmol, 10 equiv), glycine ethyl ester hydrochloride (61.9 mg, 0.445 mmol, 1 equiv) and TCFH (249.7 mg, 0.890 mmol, 2 equiv). The resulting mixture was stirred at room temperature for 2 h. The resulting mixture was then concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with DCM:MeOH = 20:1 to afford ethyl 2- {2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'-biindazol]-1-yl]acetamido}acetate (160 mg, 67.26% yield, 90.0% purity) as a white solid. m / z = 535.2 (M+H)+. Step-2: Synthesis of {2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'- biindazol]-1-yl]acetamido} acetic acid (3) To a stirred solution of ethyl 2-{2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl- [4,6'-biindazol]-1-yl]acetamido}acetate (150 mg, 0.281 mmol, 90.0% purity, 1 equiv) in THF (2 mL):H2O (2 mL):MeOH (2 mL) was added LiOH (13.5 mg, 0.565 mmol, 2.01 equiv). The resulting mixture was stirred at room temperature for 2 h. The resulting mixture was then concentrated under reduced pressure. The residue was acidified to pH 5 with HCl (aq.1 M). The precipitated solids were collected by filtration, washed with water, and dried under vacuum to afford {2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'-biindazol]-1-yl]acetamido} acetic acid (110 mg, 77.39% yield, 90.0% purity) as a white solid. m / z = 507.2 (M+H)+. Step-3: Synthesis of ethyl 2-(2-{2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl- [4,6'-biindazol]-1-yl]acetamido}acetamido)acetate (4) To a stirred solution of {2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'- biindazol]-1-yl]acetamido}acetic acid (100 mg, 0.197 mmol, 90.0% purity, 1 equiv) in ACN (5 mL) was added NMI (162.1 mg, 1.970 mmol, 10 equiv), glycine ethyl ester hydrochloride (27.4 mg, 0.197 mmol, 1 equiv), and TCFH (110.8 mg, 0.394 mmol, 2 equiv). The resulting mixture was stirred at room temperature for 2 h. The resulting mixture was then concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with DCM:MeOH = 20:1 to afford ethyl 2-(2-{2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'-biindazol]-1- yl]acetamido}acetamido)acetate (70 mg, 59.93% yield, 85.0% purity) as a white solid. m / z = 592.3 (M+H)+. Step-4: Synthesis of (2-{2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'- biindazol]-1-yl]acetamido}acetamido)acetic acid (5) To a stirred solution of ethyl 2-(2-{2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'- methyl-[4,6'-biindazol]-1-yl]acetamido}acetamido)acetate (70 mg, 0.118 mmol, 85.0% purity, 1 equiv) in THF (1 mL):H2O (1 mL):MeOH (1 mL) was added LiOH (5.7 mg, 0.236 mmol, 2 equiv). The resulting mixture was stirred at room temperature for 2 h. The resulting mixture was then concentrated under reduced pressure. The residue was acidified to pH 5 with HCl (aq. 1 M). The precipitated solids were collected by filtration, washed with water, and dried under vacuum to afford (2-{2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'-biindazol]-1- yl]acetamido}acetamido)acetic acid (60 mg, 89.98% yield, 92.0% purity) as a white solid. m / z = 564.2 (M+H)+. Step-5: Synthesis of 2-{2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H- [4,6'-biindazol]-1-yl]acetamido}-N-(carbamoylmethyl)acetamide (6) To a stirred solution of (2-{2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'- biindazol]-1-yl]acetamido}acetamido)acetic acid (70 mg, 0.124 mmol, 92.0% purity, 1 equiv) in ACN (5 mL) was added NMI (102.0 mg, 1.240 mmol, 10 equiv), NH4Cl (6.6 mg, 0.124 mmol, 1 equiv), and TCFH (69.7 mg, 0.248 mmol, 2 equiv). The resulting mixture was stirred at room temperature for 2 h. The resulting mixture was concentrated under reduced pressure. The residue was purified by reverse phase column chromatography with ACN:H2O (1:3) to afford 2-{2-[3-(1- acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl]acetamido}-N- (carbamoylmethyl)acetamide (58.0 mg, 79.68% yield, 96.0% purity) as a white solid. LCMS for C28H31FN8O4required: 562.2, found Rt= 1.329 min, m / z: 563.2 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.49 – 8.37 (m, 1H), 8.15 (d, J = 12.4 Hz, 2H), 7.83 (d, J = 5.6 Hz, 1H), 7.77 – 7.68 (m, 1H), 7.65 (d, J = 8.4 Hz, 1H), 7.53 – 7.45 (m, 1H), 7.26 (s, 1H), 7.17 – 7.04 (m, 2H), 5.17 (s, 2H), 4.26 (d, J = 12.4 Hz, 1H), 4.09 (d, J = 1.6 Hz, 4H), 3.82 (d, J = 5.6 Hz, 2H), 3.79 – 3.64 (m, 3H), 2.37 – 1.96 (m, 1H), 1.89 (d, J = 12.8 Hz, 3H), 1.78 – 1.56 (m, 2H), 1.45 (d, J = 4.2 Hz, 2H), 1.34 – 1.16 (m, 1H). Example 5 Synthesis of 2-(2-{2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl]-N-methylacetamido}acetamido)acetic acid

[0056] Step-1: Synthesis of tert-butyl 4-((2-bromo-6- fluorophenyl)(hydroxy)methyl)piperidine-1-carboxylate (2) To a stirred solution of 1-bromo-3-fluoro-2-iodobenzene (14 g, 80.460 mmol, 1 equiv) in THF (150 mL) was added dropwise LDA (2 M, 44 mL, 88.0 mmol, 1.1 equiv) at -78 °C under a nitrogen atmosphere. The resulting mixture was stirred at -78 °C under the nitrogen atmosphere for one hour. Then tert-butyl 4-formylpiperidine-1-carboxylate (34.32 g, 160.920 mmol, 2 equiv) in THF (50 mL) was added to the above mixture. The resulting mixture was stirred at -78 °C under the nitrogen atmosphere for one hour. The mixture was then quenched with water. The resulting solution was concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with PE:EtOAc = 1:1 to afford tert-butyl 4-((2-bromo-6- fluorophenyl)(hydroxy)methyl)piperidine-1-carboxylate (25.86 g, 82.78% yield, 90.0% purity) as a yellow oil. m / z = 388.1 (M+H)+. Step-2: Synthesis of tert-butyl 4-(2-bromo-6-fluorobenzoyl)piperidine-1- carboxylate (3) To a stirred solution of tert-butyl 4-((2-bromo-6- fluorophenyl)(hydroxy)methyl)piperidine-1-carboxylate (25 g, 64.387 mmol, 90.0% purity, 1 equiv) in DCM (100 mL) was added PCC (27.76 g, 128.774 mmol, 2 equiv). The resulting mixture was stirred at room temperature overnight. The resulting mixture was then concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with PE:EtOAc = 3:1 to afford tert-butyl 4-(2-bromo-6-fluorobenzoyl)piperidine-1-carboxylate (18.85 g, 75.79% yield, 85.0% purity) as a yellow solid. m / z = 386.1 (M+H)+. Step-3: Synthesis of tert-butyl 4-(4-bromo-1H-indazol-3-yl)piperidine-1- carboxylate (4) To a stirred solution of tert-butyl 4-(2-bromo-6-fluorobenzoyl)piperidine-1- carboxylate (16.85 g, 43.623 mmol, 85.0% purity, 1 equiv) in dioxane (50 mL) was added N2H4·H2O (10.92 g, 218.115 mmol, 5 equiv). The resulting mixture was stirred at 110 °C for 2 h. The resulting mixture was then concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with PE:EtOAc = 1:1 to afford tert-butyl 4-(4-bromo- 1H-indazol-3-yl)piperidine-1-carboxylate (11 g, 66.31% yield, 88.0% purity) as a yellow solid. m / z = 380.1 (M+H)+. Step-4: Synthesis of tert-butyl 4-(4-bromo-1-(2-ethoxy-2-oxoethyl)-1H-indazol-3- yl)piperidine-1-carboxylate (5) To a stirred solution of tert-butyl 4-(4-bromo-1H-indazol-3-yl)piperidine-1- carboxylate (1 g, 2.630 mmol, 88.0% purity, 1 equiv) in DMF (10 mL) was added K2CO3 (0.73 g, 5.260 mmol, 2 equiv) and ethyl bromoacetate (0.44 g, 2.630 mmol, 1 equiv). The resulting mixture was stirred at 80 °C under a nitrogen atmosphere for 4 h. The resulting solution was then diluted with water and extracted with ethyl acetate. The organic layers were combined and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with PE:EtOAc = 2:1 to afford tert-butyl 4-(4-bromo-1-(2-ethoxy-2-oxoethyl)-1H-indazol-3- yl)piperidine-1-carboxylate (800 mg, 65.57% yield, 90.0% purity) as a white solid. m / z = 466.1 (M+H)+. Step-5: Synthesis of tert-butyl 4-[1-(2-ethoxy-2-oxoethyl)-5'-fluoro-1'-methyl- [4,6'-biindazol]-3-yl]piperidine-1-carboxylate (6) To a stirred solution of tert-butyl 4-(4-bromo-1-(2-ethoxy-2-oxoethyl)-1H-indazol- 3-yl)piperidine-1-carboxylate (300 mg, 0.643 mmol, 90.0% purity, 1 equiv) in dioxane (5 mL):H2O (1 mL) was added K2CO3 (240.03 g, 1.736 mmol, 2 equiv), 5-fluoro-1-methyl-6- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indazole (335.6 mg, 1.215 mmol, 1.89 equiv), and Pd(dppf)Cl2·CH2Cl2(57.6 mg, 0.071 mmol, 0.10 equiv). The resulting mixture was stirred at 75 °C under a nitrogen atmosphere for 2 h. The resulting mixture was then concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with PE:EtOAc = 5:1 to afford tert-butyl 4-[1-(2-ethoxy-2-oxoethyl)-5'-fluoro-1'-methyl-[4,6'-biindazol]-3- yl]piperidine-1-carboxylate (370 mg, 93.19% yield, 90.0% purity) as a light yellow solid. m / z = 536.2 (M+H)+. Step-6: Synthesis of 2-[5'-fluoro-1'-methyl-3-(piperidin-4-yl)-[4,6'-biindazol]-1- yl]acetate (7) To a stirred solution of tert-butyl 4-[1-(2-ethoxy-2-oxoethyl)-5'-fluoro-1'-methyl- [4,6'-biindazol]-3-yl] piperidine-1-carboxylate (370 mg, 0.691 mmol, 90.0% purity, 1 equiv) in DCM (5 mL) was added HCl (gas) in 1,4-dioxane (4 M, 5 mL). The resulting mixture was stirred at room temperature for 2 h. The resulting mixture was then concentrated under reduced pressure to afford ethyl 2-[5'-fluoro-1'-methyl-3-(piperidin-4-yl)-[4,6'-biindazol]-1-yl]acetate (250 mg, 83.00% yield, 90.0% purity) as a light yellow solid. m / z = 436.2 (M+H)+. Step-7: Synthesis of ethyl 2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'- biindazol]-1-yl]acetate (8) To a stirred solution of ethyl 2-[5'-fluoro-1'-methyl-3-(piperidin-4-yl)-[4,6'- biindazol]-1-yl]acetate (250 mg, 0.620 mmol, 90.0% purity, 1 equiv) in DCM (5 mL) at 0 °C was added TEA (186.9 mg, 1.848 mmol, 2.98 equiv) and acetyl chloride (72.3 mg, 0.918 mmol, 1.48 eq). The resulting mixture was then stirred at room temperature under a nitrogen atmosphere for 1.5 h. The resulting mixture was then concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with PE:EtOAc = 5:1 to afford ethyl 2-[3-(1- acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'-biindazol]-1-yl]acetate (280 mg, 91.33% yield, 88.0% purity) as a light yellow solid. m / z = 478.2 (M+H)+. Step-8: Synthesis of [3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'- biindazol]-1-yl]acetic acid (9) To a stirred solution of ethyl 2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl- [4,6'-biindazol]-1-yl]acetate (255 mg, 0.534 mmol, 88.0% purity, 1 equiv) in THF (2 mL):H2O (2 mL):MeOH (2 mL) at 0 °C was added LiOH·H2O (63.8 mg, 1.522 mmol, 2.85 equiv). The resulting mixture was then stirred at room temperature overnight. The resulting mixture was then concentrated under reduced pressure. The residue was acidified to pH 5 with HCl (aq.1 M). The precipitated solids were collected by filtration, washed with water, and dried under reduced pressure to afford [3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'-biindazol]-1-yl]acetic acid (120 mg, 50.00% yield, 90.0% purity) as a light yellow solid. m / z = 450.2 (M+H)+. Step-9: Synthesis of methyl 2-{2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl- [4,6'-biindazol]-1-yl]-N-methylacetamido}acetate (10) To a stirred solution of [3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'- biindazol]-1-yl]acetic acid (120 mg, 0.267 mmol, 90.0% purity, 1.00 equiv) in DMF (5 mL) was added methyl 2-(methylamino)acetate hydrochloride (37.1 mg, 0.267 mmol, 1 equiv), HATU (152.2 mg, 0.401 mmol, 1.5 equiv), and DIEA (172.5 mg, 1.335 mmol, 5 equiv). The resulting mixture was stirred at room temperature for 1.5 h. The resulting solution was then diluted with water and extracted with ethyl acetate. The organic layers were combined and concentrated under reduced pressure. The residue was purified by reverse phase column chromatography with ACN:H2O (1:3) to afford methyl 2-{2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'- biindazol]-1-yl]-N-methylacetamido}acetate (140 mg, 95.10% yield, 85.0% purity) as a white solid. m / z = 535.2 (M+H)+. Step-10: Synthesis of {2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'- biindazol]-1-yl]-N-methylacetamido}acetic acid (11) To a stirred solution of methyl 2-{2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'- methyl-[4,6'-biindazol]-1-yl]-N-methylacetamido}acetate (150 mg, 0.281 mmol, 85.0% purity, 1 equiv) in THF (2 mL):H2O (2 mL):MeOH (2 mL) at 0 °C was added LiOH·H2O (13.4 mg, 0.562 mmol, 2 equiv). The resulting mixture was stirred at room temperature for 2 h. The resulting mixture was concentrated under reduced pressure. The residue was acidified to pH 5 with HCl (aq. 1 M). The precipitated solids were collected by filtration, washed with water, and dried under reduced pressure to afford {2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'-biindazol]-1- yl]-N-methylacetamido}acetic acid (100 mg, 68.46%, 92.0% purity) as a white solid. m / z = 521.2 (M+H)+. Step-11: Synthesis of ethyl 2-(2-{2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl- [4,6'-biindazol]-1-yl]-N-methylacetamido}acetamido)acetate (12) To a stirred solution of {2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'- biindazol]-1-yl]-N-methylacetamido}acetic acid (100 mg, 0.192 mmol, 92.0% purity, 1 equiv) in ACN (5 mL) was added NMI (157.7 mg, 1.920 mmol, 10 equiv), glycine ethyl ester hydrochloride (40 mg, 0.288 mmol, 1.5 equiv), and TCFH (80.8 mg, 0.288 mmol, 1.5 equiv). The resulting mixture was stirred at room temperature for one hour. The resulting mixture was then concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with PE:EtOAc = 1:1 to afford ethyl 2-(2-{2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'- biindazol]-1-yl]-N-methylacetamido}acetamido)acetate (80 mg, 68.76% yield, 90.0% purity) as a yellow solid. m / z = 606.3 (M+H)+. Step-12: Synthesis of 2-(2-{2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl- 1H,1'H-[4,6'-biindazol]-1-yl]-N-methylacetamido}acetamido)acetic acid (13) To a stirred solution of ethyl 2-(2-{2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'- methyl-[4,6'-biindazol]-1-yl]-N-methylacetamido}acetamido)acetate (60 mg, 0.099 mmol, 90.0% purity, 1 equiv) in THF (1 mL):H2O (1 mL):MeOH (1 mL) at 0 °C was added LiOH·H2O (4.7 mg, 0.198 mmol, 2 equiv). The resulting mixture was stirred at room temperature for 2 h. The resulting mixture was then concentrated under reduced pressure. The residue was acidified to pH 5 with HCl (aq.1 M). The resulting solution was concentrated under reduced pressure. The residue was purified by reverse phase column chromatography with ACN:H2O (1:3) to afford 2-(2-{2-[3- (1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl]-N- methylacetamido}acetamido)acetic acid (29.7 mg, 51.39% yield, 99.0% purity) as a white solid. LCMS for C29H32FN7O5 required: 577.2, found Rt = 1.504 min, m / z: 578.3 [M+H]+.1H NMR (400 MHz, Methanol-d4) δ 8.24 – 7.99 (m, 1H), 7.73 – 7.59 (m, 3H), 7.55 – 7.46 (m, 1H), 7.15 – 7.07 (m, 1H), 5.49 (d, J = 1.6 Hz, 1H), 5.41 (s, 1H), 4.43 (d, J = 6.4 Hz, 1H), 4.35 (s, 1H), 4.24 (d, J = 9.6 Hz, 1H), 4.17 (d, J = 1.6 Hz, 1H), 4.12 (s, 3H), 3.95 – 3.81 (m, 2H), 3.69 (d, J = 8.0 Hz, 1H), 3.29 (s, 1H), 3.01 (s, 1H), 2.74 – 2.60 (m, 1H), 2.49 – 2.15 (m, 1H), 2.01 (d, J = 8.4 Hz, 3H), 1.96 – 1.78 (m, 2H), 1.69 (d, J = 12.4 Hz, 1H), 1.63 – 1.41 (m, 2H). Example 6 Synthesis of 2-(2-{2-[1'-(1-acetylpiperidine-4-carbonyl)-5'-fluoro-1H,1'H-[4,6'- biindazol]-1-yl]acetamido}acetamido)acetic acid Step-1: Synthesis of methyl 2-[2-(2-{5'-fluoro-1'H-[4,6'-biindazol]-1- yl}acetamido)acetamido]acetate (2) To a stirred solution of {5'-fluoro-1'H-[4,6'-biindazol]-1-yl} acetic acid (180 mg, 0.580 mmol, 90.0% purity, 1 equiv) in DMF (5 mL) was added methyl 2-(2- aminoacetamido)acetate hydrochloride (158.9 mg, 0.870 mmol, 1.5 equiv), HATU (330.9 mg, 0.870 mmol, 1.5 equiv), and DIEA (374.9 mg, 2.900 mmol, 5 equiv). The resulting mixture was stirred at room temperature for 2 h. The resulting solution was then diluted with water and extracted with ethyl acetate. The organic layers were combined and concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18; mobile phase, MeCN in Water (10 mmol / L NH4HCO3), 20% to 40% gradient in 20 min; detector, UV 220 nm, to afford methyl 2-[2-(2-{5'-fluoro-1'H-[4,6'-biindazol]- 1-yl}acetamido)acetamido]acetate (140 mg, 55.05% yield, 90.0% purity) as a yellow solid. m / z = 439.1 (M+H)+. Step-2: Synthesis of [2-(2-{5'-fluoro-1'H-[4,6'-biindazol]-1- yl}acetamido)acetamido]acetic acid (3) To a stirred solution of methyl 2-[2-(2-{5'-fluoro-1'H-[4,6'-biindazol]-1- yl}acetamido)acetamido]acetate (130 mg, 0.297 mmol, 90.0% purity, 1 equiv) in THF (2 mL):H2O (2 mL):MeOH (2 mL) at 0 °C was added LiOH (14.2 mg, 0.594 mmol, 2 equiv). The resulting mixture was then stirred at room temperature for 2 h. The resulting mixture was then concentrated under reduced pressure. The residue was acidified to pH 5 with HCl (aq., 1 M). The precipitated solids were collected by filtration, washed with water, and dried under vacuum to afford [2-(2-{5'-fluoro-1'H-[4,6'-biindazol]-1-yl}acetamido)acetamido]acetic acid (100 mg, 79.47% yield, 90.0% purity) as a yellow solid. m / z = 425.1 (M+H)+. Step-3: Synthesis of 2-(2-{2-[1'-(1-acetylpiperidine-4-carbonyl)-5'-fluoro-1H,1'H- [4,6'-biindazol]-1-yl]acetamido}acetamido)acetic acid (4) To a stirred solution of [2-(2-{5'-fluoro-1'H-[4,6'-biindazol]-1- yl}acetamido)acetamido]acetic acid (100 mg, 0.236 mmol, 90.0% purity, 1 equiv) in DMF (5 mL) was added 1-acetylpiperidine-4-carboxylic acid (40.34 mg, 0.236 mmol, 1 equiv), HOBT (47.8 mg, 0.354 mmol, 1.5 equiv), EDCI (67.8 mg, 0.354 mmol, 1.5 equiv), and DIEA (152.27 mg, 1.180 mmol, 5 equiv). The resulting mixture was stirred at room temperature for 2 h. The resulting solution was then diluted with water and extracted with ethyl acetate. The organic layers were combined and concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, Xselect CSH OBD; mobile phase, ACN in water (formic acid (FA) 0.1%), 23% to 33% gradient in 10 min; detector, UV 254 nm, to afford 2-(2-{2-[1'-(1-acetylpiperidine-4-carbonyl)-5'-fluoro-1H,1'H-[4,6'-biindazol]-1- yl]acetamido}acetamido)acetic acid (12.2 mg, 8.92% yield, 99.5% purity) as a white solid. LCMS for C28H28FN7O6required: 577.2, found Rt= 1.391 min, m / z: 578.2 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 12.61 (s, 1H), 8.62 (s, 1H), 8.58 – 8.48 (m, 2H), 8.36 – 8.22 (m, 1H), 8.07 – 7.92 (m, 2H), 7.74 (d, J = 8.4 Hz, 1H), 7.58 – 7.50 (m, 1H), 7.31 (d, J = 7.2 Hz, 1H), 5.25 (s, 2H), 4.44 (d, J = 13.2 Hz, 1H), 4.04 – 3.89 (m, 2H), 3.86 – 3.71 (m, 4H), 3.30 – 3.08 (m, 1H), 2.83 – 2.68 (m, 1H), 2.03 (s, 5H), 1.81 – 1.68 (m, 1H), 1.60 – 1.50 (m, 1H). Example 7 Synthesis of 2-{2-[2-(1H-indazol-1-yl)acetamido]acetamido}acetic acid Step-1: ethyl 2-(1H-indazol-1-yl)acetate Indazole (1.55 g, 13.1201 mmol) and potassium carbonate (3.63 g, 26.2403 mmol) were added to a 100 mL round-bottomed flask. DMF (25.00 mL) was added followed by ethyl bromoacetate (1.60 mL, 2.41 g, 14.4322 mmol). The flask was fitted with a reflux condenser and stirred in a mantle that was heated to 70 °C. The mixture was stirred for one hour. LCMS showed some starting material with two products showing the desired mass. The mixture was then cooled to room temperature, filtered, and concentrated. The crude was purified on a 24 g silica gel column (gradient 0-50% EtOAc:hexanes). Fractions containing the first peak (least polar) with the desired mass were concentrated yielding ethyl 2-(indazol-1-yl)acetate (1.216 g, 44.47%). LCMS (ESI) m / z: 205.3 [M+H]+.1H NMR (500 MHz, CDCl3) δ 8.06 (d, J = 1.0 Hz, 1H), 7.75 (dt, J = 8.1, 1.0 Hz, 1H), 7.41 (ddd, J = 8.4, 6.8, 1.1 Hz, 1H), 7.34 (dq, J = 8.5, 0.9 Hz, 1H), 7.18 (ddd, J = 7.9, 6.8, 0.9 Hz, 1H), 5.16 (s, 2H), 4.22 (q, J = 7.1 Hz, 2H), 1.25 (td, J = 7.2, 4.9 Hz, 4H). Step-2: indazol-1-ylacetic acid A 100 mL round-bottomed flask containing ethyl 2-(indazol-1-yl)acetate (1.15 g, 5.6309 mmol) was charged with lithium hydroxide monohydrate (6.55 mL, 1.10 g, 26.2154 mmol) and THF (6.00 mL). The mixture was stirrred overnight at room temperature. Significant white precipitate was observed. The pH was adjusted to 4 with saturated aqueous citric acid solution and ethyl acetate (30 mL) while stirring rapidly. The precipitate became a finely divided suspension. The mixture was filtered and washed with water (40 mL). The precipitate was dried on the vacuum filter for thirty minutes yielding the title compound (0.678 g, 68.34%). LCMS (ESI) m / z: 177.3 [M+H]+. Step-3: {2-[2-(indazol-1-yl)acetamido]acetamido}acetic acid Indazol-1-ylacetic acid (20.00 mg, 0.1135 mmol), [(dimethylamino)({[1,2,3]triazolo[4,5-b]pyridin-3- yloxy})methylidene]dimethylazanium; hexafluoro-lambda5-phosphanuide (43.17 mg, 0.1135 mmol), and DMF (0.3 mL)were added to a 1-dram vial. N,N-diisopropylethylamine (79.31 µL, 58.69 mg, 0.4541 mmol) was added and the mixture was stirred at room temperature for five minutes. Methyl 2-(2-aminoacetamido)acetate hydrochloride (16.59 mg, 0.1135 mmol) was added and the mixture was stirred at room temperature. LCMS after twenty minutes showed the desired product formation.150 µL of the mixture was submitted for HPLC purification yielding (0.0068 g, 19.68%) of the intermediate methyl ester. The remaining solution was treated with lithium hydroxide monohydrate (0.30 mL, 0.05 g, 1.2000 mmol) at room temperature for one hour. LCMS showed the desired product. The pH was adjusted to 4 with saturated aqueous citric acid. The crude was submitted for HPLC purification and provided {2-[2-(indazol-1- yl)acetamido]acetamido}acetic acid (0.0123 g, 37.10%). LCMS for C13H14N4O4 required: 290.1, found m / z: 291.0 [M+H]+.1H NMR (500 MHz, DMSO-d6) δ 12.21 (s, 1H), 8.44 (t, J = 5.7 Hz, 1H), 8.28 (t, J = 5.8 Hz, 1H), 8.07 (s, 1H), 7.79 – 7.73 (m, 1H), 7.59 (dt, J = 8.5, 1.0 Hz, 1H), 7.37 (ddd, J = 8.2, 6.9, 1.1 Hz, 1H), 7.14 (dd, J = 8.0, 6.9 Hz, 1H), 5.16 (s, 2H), 3.79 (t, J = 5.9 Hz, 4H). Example 8 Synthesis of 2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl]-N-{[(2H-1,2,3,4-tetrazol-5-yl)carbamoyl]methyl}acetamide Step-1: Synthesis of 2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H- [4,6'-biindazol]-1-yl]-N-{[(2H-1,2,3,4-tetrazol-5-yl)carbamoyl]methyl}acetamide (2) To a stirred solution of {2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-[4,6'- biindazol]-1-yl]acetamido} acetic acid (150 mg, 0.296 mmol, 90.0% purity, 1 equiv) in DMF (5 mL) was added PyBOP (231.2 mg, 0.444 mmol, 1.5 equiv), 2H-tetrazol-5-amine (50.4 mg, 0.591 mmol, 3 equiv), and DIEA (51.0 mg, 0.394 mmol, 2 equiv). The resulting mixture was stirred at room temperature for 2 h. The resulting solution was then diluted with water and extracted with ethyl acetate. The organic layers were combined and concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, Xcelect CSH F-pheny OBD; mobile phase, ACN in water (FA 0.1%), 30% to 40% gradient in 10 min; detector, UV 254 nm, to afford 2-[3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'- methyl-1H,1'H-[4,6'-biindazol]-1-yl]-N-{[(2H-1,2,3,4-tetrazol-5- yl)carbamoyl]methyl}acetamide (16.6 mg, 9.70% yield, 96.9% purity) as a white solid. LCMS for C27H28FN11O3 required: 573.2, found Rt = 1.508 min, m / z: 574.3.1H NMR (300 MHz, DMSO-d6) δ 12.06 (s, 1H), 8.73 – 8.49 (m, 1H), 8.14 (s, 1H), 7.82 (d, J = 5.7 Hz, 1H), 7.76 – 7.69 (m, 1H), 7.65 (d, J = 8.4 Hz, 1H), 7.55 – 7.43 (m, 1H), 7.10 (d, J = 6.9 Hz, 1H), 5.20 (s, 2H), 4.27 (d, J = 13.2 Hz, 1H), 4.09 (d, J = 5.7 Hz, 5H), 3.81 – 3.49 (m, 1H), 3.31 (s, 1H), 2.35 – 2.20 (m, 1H), 2.11 – 1.84 (m, 3H), 1.78 – 1.59 (m, 2H), 1.52 – 1.38 (m, 2H), 1.35 – 1.11 (m, 1H). Example 9 Synthesis of 2-(2-{2-[3-(1-acetylazetidin-3-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl]acetamido}acetamido)acetic acid Step-1: Synthesis of tert-butyl 3-((2-bromo-6- fluorophenyl)(hydroxy)methyl)azetidine-1-carboxylate (2) To a stirred solution of m-bromofluorobenzene (2 g, 11.429 mmol, 1 equiv) in THF (30 mL) was added dropwise LDA (2 M, 6.5 mL, 13.0 mmol, 1.13 equiv) at -78 °C under a nitrogen atmosphere. The resulting mixture was stirred at -78 °C under the nitrogen atmosphere for one hour. Then tert-butyl 3-formylazetidine-1-carboxylate (4.23 g, 22.858 mmol, 2 equiv) in THF (5 mL) was added dropwise to the resulting solution. The resulting mixture was stirred at -78 °C under the nitrogen atmosphere for one hour. The mixture was then quenched with water. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with PE:EtOAc = 1:1 to afford tert-butyl 3-((2-bromo-6-fluorophenyl)(hydroxy)methyl)azetidine-1-carboxylate (2.3 g, 55.87% yield, 90.0% purity) as a yellow oil. m / z = 360.0 (M+H)+. Step-2: Synthesis of tert-butyl 3-(2-bromo-6-fluorobenzoyl)azetidine-1- carboxylate (3) To a stirred solution of tert-butyl 3-((2-bromo-6- fluorophenyl)(hydroxy)methyl)azetidine-1-carboxylate (1.29 g, 3.581 mmol, 90.0% purity, 1 equiv) in DCM (20 mL) was added PCC (1.54 g, 7.162 mmol, 2 equiv). The resulting mixture was stirred at room temperature overnight. The resulting mixture was then concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with PE:EtOAc = 3:1 to afford tert-butyl 3-(2-bromo-6-fluorobenzoyl)azetidine-1-carboxylate (1.1 g, 85.75% yield, 90.0% purity) as a yellow solid. m / z = 358.0 (M+H)+. Step-3: Synthesis of tert-butyl 3-(4-bromo-1H-indazol-3-yl)azetidine-1- carboxylate (4) To a stirred solution of tert-butyl 3-(2-bromo-6-fluorobenzoyl)azetidine-1- carboxylate (1.1 g, 3.071 mmol, 90.0% purity, 1 equiv) in dioxane (10 mL) was added N2H4·H2O (0.77 g, 15.355 mmol, 5 equiv). The resulting mixture was stirred at 110 °C for 2 h. The resulting mixture was then concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with PE:EtOAc = 1:1 to afford tert-butyl 3-(4-bromo-1H-indazol- 3-yl)azetidine-1-carboxylate (900 mg, 83.21% yield, 85.0% purity) as a yellow solid. m / z = 352.0 (M+H)+. Step-4: Synthesis of tert-butyl 3-[4-bromo-1-(2-ethoxy-2-oxoethyl)indazol-3- yl]azetidine-1-carboxylate (5) To a stirred solution of tert-butyl 3-(4-bromo-1H-indazol-3-yl)azetidine-1- carboxylate (880 mg, 2.498 mmol, 85.0% purity, 1 equiv) in DMF (10 mL) was added K2CO3(690.6 mg, 4.996 mmol, 2 equiv) and ethyl bromoacetate (417.2 mg, 2.498 mmol, 1 equiv). The resulting mixture was stirred at 80 °C under a nitrogen atmosphere for 2 h. The resulting solution was then diluted with water and extracted with ethyl acetate. The organic layers were combined and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with PE:EtOAc = 2:1 to afford tert-butyl 3-[4-bromo-1-(2-ethoxy-2- oxoethyl)indazol-3-yl]azetidine-1-carboxylate (900 mg, 82.19% yield, 90.0% purity) as a yellow oil. m / z = 438.1 (M+H)+. Step-5: Synthesis of ethyl 2-[3-(azetidin-3-yl)-4-bromoindazol-1-yl]acetate (6) To a stirred solution of tert-butyl 3-[4-bromo-1-(2-ethoxy-2-oxoethyl)indazol-3- yl]azetidine-1-carboxylate (900 mg, 2.053 mmol, 90.0% purity, 1 equiv) in DCM (8 mL) was added HCl (gas) in 1,4-dioxane (8 mL, 4 M) at 0 °C. The resulting mixture was then stirred at room temperature for 2 h. The resulting mixture was then concentrated under reduced pressure to afford ethyl 2-[3-(azetidin-3-yl)-4-bromoindazol-1-yl]acetate (610 mg, 90.00% yield, 90.0% purity) as a light yellow solid. m / z = 338.0 (M+H)+. Step-6: Synthesis of ethyl 2-[3-(1-acetylazetidin-3-yl)-4-bromoindazol-1- yl]acetate (7) To a stirred solution of ethyl 2-[3-(azetidin-3-yl)-4-bromoindazol-1-yl]acetate (800 mg, 2.365 mmol, 90.0% purity, 1 equiv) in DCM (5 mL) at 0 °C was added TEA (478.73 mg, 4.730 mmol, 2 equiv) and acetyl chloride (278.53 mg, 3.548 mmol, 1.5 equiv). The resulting mixture was then stirred at room temperature for 1.5 h. The resulting mixture was then concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with DCM:MeOH = 20:1 to afford ethyl 2-[3-(1-acetylazetidin-3-yl)-4- bromoindazol-1-yl]acetate (500 mg, 55.59% yield, 88.0% purity) as a yellow solid. m / z = 380.0 (M+H)+. Step-7: Synthesis of ethyl 2-[3-(1-acetylazetidin-3-yl)-5'-fluoro-1'-methyl-[4,6'- biindazol]-1-yl]acetate (8) To a stirred solution of ethyl 2-[3-(1-acetylazetidin-3-yl)-4-bromoindazol-1- yl]acetate (200 mg, 0.526 mmol, 88.0% purity, 1 equiv) in dioxane (5 mL):H2O (1 mL) was added 5-fluoro-1-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indazole (246.9 mg, 0.894 mmol, 1.7 equiv), K2CO3 (159.9 mg, 1.157 mmol, 2.2 equiv), and Pd(dppf)Cl2·CH2Cl2 (42.9 mg, 0.053 mmol, 0.1 equiv). The resulting mixture was stirred at 75 °C under a nitrogen atmosphere for 2 h. The resulting mixture was then concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with DCM:MeOH = 15:1 to afford ethyl 2- [3-(1-acetylazetidin-3-yl)-5'-fluoro-1'-methyl-[4,6'-biindazol]-1-yl]acetate (200 mg, 84.59% yield, 90.0% purity) as a brown solid. m / z = 451.0 (M+H)+. Step-8: Synthesis of [3-(1-acetylazetidin-3-yl)-5'-fluoro-1'-methyl-[4,6'- biindazol]-1-yl]acetic acid (9) To a stirred solution of ethyl 2-[3-(1-acetylazetidin-3-yl)-5'-fluoro-1'-methyl-[4,6'- biindazol]-1-yl]acetate (200 mg, 0.445 mmol, 90.0% purity, 1 equiv) in THF (5 mL):H2O (5 mL):MeOH (5 mL) at 0°C was added LiOH (21.3 mg, 0.890 mmol,...

Claims

WHAT IS CLAIMED IS:

1. A compound having the following formula or a pharmaceutically acceptable salt thereof, wherein is selected from the group consisting of an aryl, heteroaryl, bicyclic aryl, and bicyclic heteroaryl wherein aryl, heteroaryl, bicyclic aryl, and bicyclic heteroaryl are unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, halo, or heteroaryl; R1is , , , , , , , , , or ; or each R1is further substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, halo, or heteroaryl, wherein R5is independently hydrogen or alkyl; R6is hydrogen or an amino acid side chain; R7is –OR7a, –NR7aR7b, or , wherein R7aand R7bare independently hydrogen or alkyl; aa is one to five; R8is heteroalkyl; R9is aryl, benzo[d][1,3]dioxole, heteroalkyl, or heteroaryl comprising at least one nitrogen, oxygen, or sulfur wherein the aryl and heteroaryl are unsubstituted orsubstituted with alkyl, –OH, hydroxyalkyl, alkoxy, cyano, pyridazine, and pyrazole; R10is hydrogen, alkyl, or hydroxyalkyl; R11is heteroaryl wherein heteroaryl is unsubstituted or substituted with alkyl, haloalkyl, alkoxy, –OH, –C(O)NR11aR11b, or , wherein R11aand R11bare independently hydrogen or alkyl; X6is oxygen or NR5; t1is one to five; t2is zero or one; R3is hydrogen, , aryl, or heteroaryl, wherein aryl or heteroaryl are unsubstituted or substituted with alkyl, heteroalkyl, heterocycloalkyl, and / or halo; X5is nitrogen or oxygen; R3ais hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, five- to fifteen-membered spiro bicyclic heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl; –C(O)-(three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl); three- to -eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl;-alkylene-(three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl); -alkylene-N(R3aa)C(O)alkyl wherein R3aais hydrogen or alkyl; or absent when X5is oxygen; R3bis hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl; and R3crepresents one, two, or three hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, cyano, alkoxy, or halo.

2. A compound having the following formula or a pharmaceutically acceptable salt thereof, wherein is ; ; ; ; ; or ; wherein X1is CH, C-OH, C-alkyl, C-alkoxy, C-haloalkoxy, or nitrogen; X1ais CH, C-OH, C-alkyl, C-alkoxy, C-haloalkoxy, or nitrogen;X2is CH, C-OH, C-alkyl, C-alkoxy, C-haloalkoxy, or nitrogen; X3is carbon or nitrogen; X4is nitrogen or oxygen; Y is CH or nitrogen; is a single bond or a double bond; R1is , , , , , , , , , or ; or each R1is further substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, halo, or heteroaryl, wherein each R1ais independently -CH2- or -C(O)- and R1bis independently -CH2- or -NH-; R5is independently hydrogen alkyl, or cycloalkyl; R6is hydrogen or an amino acid side chain; R7is –OR7a, –NR7aR7b, or , wherein R7aand R7bare independently hydrogen or alkyl; aa is one to five; R8is heteroalkyl; R9is , , or , whereinis aryl or heteroaryl, wherein aryl or heteroaryl is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, halo, or heteroaryl; each R9ais independently hydrogen or alkyl; R9bis -C(O)OR9cor ; each R9cis hydrogen or C1-5alkyl; and bb is one or two; cc is zero, one, or two; aryl, benzo[d][1,3]dioxole, heteroalkyl, or heteroaryl comprising at least one nitrogen, oxygen, or sulfur wherein the aryl and heteroaryl are unsubstituted or substituted with alkyl, –OH, hydroxyalkyl, alkoxy, cyano, pyridazine, and pyrazole; R10is hydrogen, alkyl, or hydroxyalkyl; R11is heteroaryl wherein heteroaryl is unsubstituted or substituted with alkyl, haloalkyl, alkoxy, –OH, –C(O)NR11aR11b, or , wherein R11aand R11bare independently hydrogen or alkyl; X6is oxygen or NR5; t1is one to five; t2is zero or one; R2is, independently, one to three of hydrogen, –OH, –SH, –S-alkyl, –NR7aR7b, alkyl, alkoxy, or haloalkoxy; R3, when present, is hydrogen, , , aryl, or heteroaryl, wherein aryl or heteroaryl are unsubstituted or substituted with alkyl, heteroalkyl, heterocycloalkyl, and / or halo; X5is nitrogen or oxygen;R3ais hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, five- to fifteen-membered spiro bicyclic heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl; –C(O)-(three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, or –C(O)-alkylene-C(O)R3aaawherein R3aaais –OR7a, –NR7aR7bor alkyl); three- to -eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl; -alkylene-(three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl); -alkylene-N(R3aa)C(O)alkyl wherein R3aais hydrogen or alkyl; –C(O)-alkylene-C(O)R3aaawherein R3aaais –OR7a, –NR7aR7bor alkyl; or absent when X5is oxygen; R3bis hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl; R3crepresents one, two, or three hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, cyano, alkoxy, or halo; R4, when present, is hydrogen, alkyl, haloalkyl, arylalkyl, aryl, heteroaryl, or heterocycloalkyl, wherein aryl, heteroaryl, or heterocycloalkyl are unsubstituted or substituted with alkyl, alkenyl, alkynyl, heteroalkyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, –C(O)-alkylene-C(O)R3aaawherein R3aaais–OR7a, –NR7aR7bor alkyl; or –C(O)NR4aR4bwherein R4aand R4bare independently hydrogen or alkyl; a five- to fifteen-membered spiro bicyclic heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, or –C(O)-alkylene-C(O)R3aaawherein R3aaais –OR7a, –NR7aR7bor alkyl; –NR4aR4bwherein R4aand R4bare independently hydrogen, alkyl, aryl, heteroaryl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, or arylalkyl; three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl, –C(O)-heteroalkylene-NR4aR4b, alkyl, –C(O)-alkylene-COOR5, –C(O)-alkylene-C(O)NR4aR4b, –C(O)-alkylene-C(O)N(R4a)-heteroalkylene-halo, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl, wherein R4aand R4bare independently hydrogen, alkyl, or acyl; -alkylene-NR4aR4bwherein R4aand R4bare independently hydrogen, alkyl, or acyl; or –N(R5)C(O)-alkylene-NR4aR4bwherein R4aand R4bare independently hydrogen, alkyl, or acyl.

3. A compound having the following formula or a pharmaceutically acceptable salt thereof, whereinis ; ; ; ; or ; wherein X1is CH, C-OH, C-alkyl, C-alkoxy, C-haloalkoxy, or nitrogen; X1ais CH, C-OH, C-alkyl, C-alkoxy, C-haloalkoxy, or nitrogen; X2is CH, C-OH, C-alkyl, C-alkoxy, C-haloalkoxy, or nitrogen; X3is carbon or nitrogen; X4is nitrogen or oxygen; Y is CH or nitrogen; is a single bond or a double bond; R1is , , , , , , , , , or ; or each R1is further substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, halo, or heteroaryl, whereineach R1ais independently -CH2- or -C(O)- and R1bis independently -CH2- or -NH-; R5is independently hydrogen or alkyl; R6is hydrogen or an amino acid side chain; R7is –OR7a, –NR7aR7b, or , wherein R7aand R7bare independently hydrogen or alkyl; aa is one to five; R8is heteroalkyl; R9is aryl, benzo[d][1,3]dioxole, heteroalkyl, or heteroaryl comprising at least one nitrogen, oxygen, or sulfur wherein the aryl and heteroaryl are unsubstituted or substituted with alkyl, –OH, hydroxyalkyl, alkoxy, cyano, pyridazine, and pyrazole; R10is hydrogen, alkyl, or hydroxyalkyl; R11is heteroaryl wherein heteroaryl is unsubstituted or substituted with alkyl, haloalkyl, alkoxy, –OH, –C(O)NR11aR11b, or , wherein R11aand R11bare independently hydrogen or alkyl; X6is oxygen or NR5; t1is one to five; t2is zero or one; R2is, independently, one to three of hydrogen, –OH, alkyl, alkoxy, or haloalkoxy; R3, when present, is hydrogen, , aryl, or heteroaryl, wherein aryl or heteroaryl are unsubstituted or substituted with alkyl, heteroalkyl, heterocycloalkyl, and / or halo; X5is nitrogen or oxygen; R3ais hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, five- to fifteen-membered spiro bicyclic heterocycloalkyl comprising at least one nitrogen, wherein the atleast one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl; –C(O)-(three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl); three- to -eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl; -alkylene-(three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl); -alkylene-N(R3aa)C(O)alkyl wherein R3aais hydrogen or alkyl; or absent when X5is oxygen; R3bis hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl; R3crepresents one, two, or three hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, cyano, alkoxy, or halo; R4, when present, is hydrogen, alkyl, haloalkyl, arylalkyl, aryl, heteroaryl, or heterocycloalkyl, wherein aryl, heteroaryl, or heterocycloalkyl are unsubstituted or substituted with alkyl, alkenyl, alkynyl, heteroalkyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, or –C(O)NR4aR4bwherein R4aand R4bare independently hydrogen or alkyl; a five- to fifteen-membered spiro bicyclic heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl;–NR4aR4bwherein R4aand R4bare independently hydrogen, alkyl, aryl, heteroaryl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, or arylalkyl; three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl, –C(O)-heteroalkylene-NR4aR4b, alkyl, –C(O)-alkylene-COOR5, –C(O)-alkylene-C(O)NR4aR4b, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl, wherein R4aand R4bare independently hydrogen, alkyl, or acyl; -alkylene-NR4aR4bwherein R4aand R4bare independently hydrogen, alkyl, or acyl; or –N(R5)C(O)-alkylene-NR4aR4bwherein R4aand R4bare independently hydrogen, alkyl, or acyl.

4. The compound of claim 3, wherein is ; R3, when present, is ; and R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl, –C(O)-heteroalkylene-NR4aR4b, alkyl, –C(O)-alkylene-COOR5, –C(O)-alkylene-C(O)NR4aR4b, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl, wherein R4aand R4bare independently hydrogen, alkyl, or acyl.

5. The compound of claim 4, wherein R3ais alkyl; R3bis hydrogen; and R3cis one or more alkoxy or halo.

6. The compound of claim 5, wherein R3is , , , , or .

7. The compound of claim 6, wherein R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl.

8. The compound of claim 7, wherein R4is , , , , or .

9. The compound of claim 8, wherein R1is .

10. The compound of claim 9, wherein the compound is selected from the group consisting of (2-(3-(1-acetylazetidin-3-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (1), N-(2-((2H-tetrazol-5-yl)amino)-2-oxoethyl)-2-(3-(1-acetylpiperidin- 4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetamide (2), N-((2H-tetrazol-5- yl)methyl)-2-(2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetamido)acetamide (3), 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)-N-(2-((2-amino-2-oxoethyl)amino)-2-oxoethyl)acetamide (4), N-((2-(3-(1- acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycyl)-N- methylglycine (5), N-((2H-tetrazol-5-yl)methyl)-2-(2-(2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)acetamido)acetamide (6), N-(N-(2-(3-(1- acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N-methylglycyl)- N-methylglycine (7), N-(2-((5H-tetrazol-5-yl)amino)-2-oxoethyl)-2-(3-(1-acetylpiperidin-4-yl)- 5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-methylacetamide (8), (2-(5'-fluoro-1'- methyl-3-(piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (76), (2-(3-(1- acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (9), N-(2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N- methylglycylglycine (10), (2-(3-(1-acetylpiperidin-4-yl)-4-(5-fluoro-1-methyl-1H-indazol-6-yl)- 1H-pyrazolo[3,4-b]pyridin-1-yl)acetyl)glycylglycine (11), rac-(R)-(R)-(2-(3-(1-acetylazepan-4- yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (12), N-(2-(3-(1- acetylazetidin-3-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N- methylglycylglycine (13), (2-(3-(4-acetylpiperazin-1-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)acetyl)glycylglycine (14), (2-(3-(1-acetylpiperidin-4-yl)-5'-methoxy-1'-methyl- 1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (15), (2-(3-(1-acetylpiperidin-4-yl)-7'-fluoro- 1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (16), methyl (2-(5'-fluoro-1'-methyl- 3-(piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (215), tert-butyl (2-(5'- fluoro-1'-methyl-3-(piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (216), methyl (2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (217), (2-(3-(1-acetylpiperidin-4-yl)-5',7'-difluoro-1'-methyl-1H,1'H- [4,6'-biindazol]-1-yl)acetyl)glycylglycine (218), and (2-(3-(1-acetylpiperidin-4-yl)-4'-fluoro-1'- methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (17).

11. The compound of claim 8, wherein R1is .

12. The compound of claim 11, wherein the compound is selected from the group consisting of 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(4- (hydroxymethyl)-2-methylthiophen-3-yl)acetamide (18), 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro- 1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(1,6-naphthyridin-4-yl)acetamide (19), 2-(3-(1- acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(isoquinolin-4- yl)acetamide (20), 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)-N-(3-methylisoxazol-4-yl)acetamide (21), 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(1,7-naphthyridin-4-yl)acetamide (22), 2-(3-(1-acetylpiperidin- 4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(5-methylpyridin-3-yl)acetamide (23), 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(4- methylpyridin-3-yl)acetamide (24), 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H- [4,6'-biindazol]-1-yl)-N-(7-hydroxy-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)acetamide (25), 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N- (pyrazolo[1,5-a]pyridin-4-yl)acetamide (26), 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl- 1H,1'H-[4,6'-biindazol]-1-yl)-N-(pyrazolo[1,5-b]pyridazin-3-yl)acetamide (27), 2-(3-(1- acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(benzo[d][1,3]dioxol- 4-yl)acetamide (28), 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)-N-(2-(2-methoxyethoxy)ethyl)acetamide (29), 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'- methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(2-(methoxymethyl)-2H-1,2,3-triazol-4-yl)acetamide (30), N-(4-(1H-pyrazol-1-yl)pyrimidin-5-yl)-2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl- 1H,1'H-[4,6'-biindazol]-1-yl)acetamide (31), 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl- 1H,1'H-[4,6'-biindazol]-1-yl)-N-(1-(pyridazin-3-yl)-1H-pyrazol-5-yl)acetamide (32), 2-(3-(1- acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(pyrido[3,4-b]pyrazin- 8-yl)acetamide (33), 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)-N-(2,7-naphthyridin-4-yl)acetamide (34), N-([1,2,4]triazolo[1,5-a]pyridin-8-yl)-2-(3-(1- acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetamide (35), and 2-(3- (1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(3-cyano-2- methylphenyl)acetamide (36).

13. The compound of claim 8, wherein R1is .

14. The compound of claim 13, wherein the compound is selected from the group consisting of (S)-2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(2- hydroxy-1-(5-methyl-1H-1,2,4-triazol-3-yl)ethyl)acetamide (37), (R)-2-(3-(1-acetylpiperidin-4- yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-((3-(1-hydroxyethyl)-1H-1,2,4-triazol-5- yl)methyl)acetamide (38), 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)-N-((5-ethyloxazol-2-yl)methyl)acetamide (39), 2-(3-(1-acetylpiperidin-4-yl)-5'- fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-((5-(difluoromethyl)-1,24-oxadiazol-3-yl)methyl)acetamide (40), 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)-N-((2-methoxypyrimidin-4-yl)methyl)acetamide (41), 3-((2-(3-(1- acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)methyl)-1,2,4- oxadiazole-5-carboxamide (42), 2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)-N-((5-hydroxy-6-methoxypyridin-2-yl)methyl)acetamide (43), and 2-(3-(1- acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-methyl-N-((5-methyl- 1,2,4-oxadiazol-3-yl)methyl)acetamide (44).

15. The compound of claim 8, wherein R1is .

16. The compound of claim 15, wherein the compound is rac-2-(3-(1-acetylpiperidin-4-yl)- 5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-((2R,3R)-2-(1-methyl-1H-imidazol-2- yl)tetrahydrofuran-3-yl)acetamide (45).

17. The compound of claim 8, wherein R1is .

18. The compound of claim 17, wherein the compound is rac-2-(3-(1-acetylpiperidin-4-yl)- 5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-methyl-N-(((2R,3R)-3-(3-methyl-1H-1,2,4- triazol-5-yl)tetrahydrofuran-2-yl)methyl)acetamide (46).

19. The compound of claim 8, wherein the compound is 2-(3-(1-acetylpiperidin-4-yl)-5'- fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-1-(3-(hydroxymethyl)-6,7-dihydro- [1,2,3]triazolo[1,5-a]pyrazin-5(4H)-yl)ethan-1-one (47).

20. The compound of claim 8, wherein R1is .

21. The compound of claim 20, wherein the compound is N-([1,2,4]triazolo[3,4- b][1,3,4]thiadiazol-6-yl)-2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)acetamide (48).

22. The compound of claim 8, wherein R1is .

23. The compound of claim 22, wherein the compound is 2-(3-(1-acetylpiperidin-4-yl)-5'- fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-(1-methyl-4-oxo-1,4-dihydropyrimidin-2- yl)acetamide (49).

24. The compound of claim 8, wherein R1is .

25. The compound of claim 24, wherein the compound is N-(2-(2H-tetrazol-2-yl)ethyl)-2-(3- (1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetamide (50).

26. The compound of claim 4, wherein R3ais alkyl; R3bis hydrogen; and R3cis cyano.

27. The compound of claim 26, wherein R3is .

28. The compound of claim 27, wherein R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl.

29. The compound of claim 28, wherein R4is .

30. The compound of claim 29, wherein R1is .

31. The compound of claim 30, wherein the compound is (2-(3-(1-acetylpiperidin-4-yl)-5'- cyano-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (51).

32. The compound of claim 4, wherein R3ais alkyl; R3bis hydrogen; and R3cis chloro.

33. The compound of claim 32, wherein R3is .

34. The compound of claim 33, wherein R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl.

35. The compound of claim 34, wherein R4is .

36. The compound of claim 35, wherein R1is .

37. The compound of claim 36, wherein the compound is (2-(3-(1-acetylpiperidin-4-yl)-5'- chloro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (52).

38. The compound of claim 3, wherein R3ais alkyl; R3bis hydrogen; and R3cis alkyl.

39. The compound of claim 38, wherein R3is .

40. The compound of claim 39, wherein R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl.

41. The compound of claim 40, wherein R4is .

42. The compound of claim 41, wherein R1is .

43. The compound of claim 42, wherein the compound is (2-(3-(1-acetylpiperidin-4-yl)-1',5'- dimethyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (53).

44. The compound of claim 6, wherein R4, when present, is heterocycloalkyl, wherein heterocycloalkyl is unsubstituted or substituted with alkyl.

45. The compound of claim 44, wherein R4is or .

46. The compound of claim 45, wherein R1is .

47. The compound of claim 46, wherein the compound is (2-(5'-fluoro-1'-methyl-3- morpholino-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (54) or (2-(3-((2R,6S)-2,6- dimethylmorpholino)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (55).

48. The compound of claim 6, wherein R4, when present, is hydrogen, alkyl, haloalkyl, aryl, heteroaryl, or arylalkyl.

49. The compound of claim 48, R4is hydrogen, methyl, ethyl, isopropyl, trifluoromethyl, phenyl, pyridyl, or benzyl.

50. The compound of claim 49, R1is .

51. The compound of claim 50, where the compound is selected from the group consisting of (2-(5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (56), N-(2-((2H- tetrazol-5-yl)amino)-2-oxoethyl)-2-(2-(5'-fluoro-1',3-dimethyl-1H,1'H-[4,6'-biindazol]-1- yl)acetamido)acetamide (57), (2-(5'-fluoro-1',3-dimethyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (58), (2-(3-ethyl-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (59), N-(2-((2H-tetrazol-5-yl)amino)-2-oxoethyl)-2-(2-(5'-fluoro-3-isopropyl-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)acetamide (60), (2-(5'-fluoro-3- isopropyl-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (61), (2-(5'-fluoro-1'- methyl-3-(trifluoromethyl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (62), N-(2-(5'- fluoro-1'-methyl-3-(trifluoromethyl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N-methylglycylglycine (63), N-(2-((2H-tetrazol-5-yl)amino)-2-oxoethyl)-2-(2-(5'-fluoro-1'-methyl-3-(trifluoromethyl)- 1H,1'H-[4,6'-biindazol]-1-yl)acetamido)acetamide (64), (2-(5'-fluoro-1'-methyl-3-phenyl- 1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (65), (2-(5'-fluoro-1'-methyl-3-(pyridin-3-yl)- 1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (66), (2-(3-benzyl-5'-fluoro-1'-methyl-1H,1'H- [4,6'-biindazol]-1-yl)acetyl)glycylglycine (67), (2-(4-(5-fluoro-1-methyl-1H-indazol-6-yl)-1H- pyrazolo[4,3-c]pyridin-1-yl)acetyl)glycylglycine (68), and (2-(4-(5-fluoro-1-methyl-1H-indazol- 6-yl)-1H-pyrazolo[3,4-c]pyridin-1-yl)acetyl)glycylglycine (69).

52. The compound of claim 6, wherein R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with –C(O)-heteroalkylene-NR4aR4band wherein R4aand R4bare independently hydrogen, alkyl, or acyl.

53. The compound of claim 52, wherein R4is .

54. The compound of claim 53, wherein R1is .

55. The compound of claim 54, wherein the compound is selected from the group consisting of methyl (2-(3-(1-(3-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)propanoyl)piperidin-4-yl)-5'-fluoro- 1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (70) and (2-(3-(1-(3-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)propanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)acetyl)glycylglycine (71).

56. The compound of claim 6, wherein R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with –C(O)-alkylene-COOR5or –C(O)-alkylene-C(O)NR4aR4band wherein R4aand R4bare independently hydrogen, alkyl, or acyl.

57. The compound of claim 56, wherein R4is or .

58. The compound of claim 57, wherein R1is .

59. The compound of claim 58, wherein the compound is selected from the group consisting of 4-(4-(1-(2-((2-((carboxymethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-4-(5-fluoro-1-methyl- 1H-indazol-6-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)piperidin-1-yl)-4-oxobutanoic acid (72), (2-(3- (1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-4-(5-fluoro-1-methyl-1H-indazol-6-yl)-1H- pyrazolo[3,4-b]pyridin-1-yl)acetyl)glycylglycine (73), and methyl (2-(5'-fluoro-1'-methyl-3-(1- (4-(methylamino)-4-oxobutanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (229).

60. The compound of claim 6, wherein R4, when present, is –N(R5)C(O)-alkylene-NR4aR4bwherein R4aand R4bare independently hydrogen, alkyl, or acyl.

61. The compound of claim 60, wherein R4is .

62. The compound of claim 61, wherein R1is .

63. The compound of claim 62, wherein the compound is (2-(3-(3-acetamidopropanamido)- 5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (74).

64. The compound of claim 6, wherein R4, when present, is -alkylene-NR4aR4bwherein R4aand R4bare independently hydrogen, alkyl, or acyl.

65. The compound of claim 64, wherein R4is .

66. The compound of claim 65, wherein R1is .

67. The compound of claim 66, wherein the compound is (2-(3-(3-acetamidopropyl)-5'- fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (75).

68. The compound of claim 6, wherein R4, when present, is three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl.

69. The compound of claim 68, wherein R4is or .

70. The compound of claim 69, wherein R1is .

71. The compound of claim 70, wherein the compound is selected from the group consisting of (2-(5'-fluoro-1'-methyl-3-(piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (76) and (2-(5'-fluoro-1'-methyl-3-(1-methylpiperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (77).

72. The compound of claim 6, wherein R4, when present, is a five- to fifteen-membered spiro bicyclic heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl.

73. The compound of claim 72, wherein the five- to fifteen-membered spiro bicyclic heterocycloalkyl comprising at least one nitrogen is further wherein n1is zero to six, n2is zero to three, and n3is one to three.

74. The compound of claim 73, wherein R4is .

75. The compound of claim 74, wherein R1is .

76. The compound of claim 75, wherein the compound is (2-(3-(2-acetyl-2- azaspiro[3.3]heptan-6-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (78) or N-(2-(3-(2-acetyl-2-azaspiro[3.3]heptan-6-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)acetyl)-N-methylglycylglycine (79).

77. The compound of claim 6, wherein R4, when present, is –NR4aR4bwherein R4aand R4bare independently hydrogen, alkyl, aryl, heteroaryl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, or arylalkyl.

78. The compound of claim 77, wherein R4is .

79. The compound of claim 78, wherein R1is .

80. The compound of claim 79, wherein the compound is (2-(5'-fluoro-1'-methyl-3- (methyl(phenyl)amino)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (80).

81. The compound of claim 3, wherein R3ais alkyl; R3bis hydrogen; and R3cis hydrogen.

82. The compound of claim 81, wherein R3is .

83. The compound of claim 82, wherein R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl.

84. The compound of claim 83, wherein R4is .

85. The compound of claim 84, wherein R1is .

86. The compound of claim 85, wherein the compound is selected from the group consisting of (2-(3-(1-acetylpiperidin-4-yl)-1'-methyl-1H,1'H-[4,5'-biindazol]-1-yl)acetyl)glycylglycine (81) and (2-(3-(1-acetylpiperidin-4-yl)-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (82).

87. The compound of claim 4, wherein R3ais a five- to fifteen-membered spiro bicyclic heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl; –C(O)-(three- to -eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl); three- to -eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl;-alkylene-(three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl); or an -alkylene-N(R3aa)C(O)alkyl wherein R3aais hydrogen or alkyl; R3bis hydrogen; and R3cis fluoro.

88. The compound of claim 87, wherein R3is , , , , or .

89. The compound of claim 88, wherein R4, when present, is hydrogen or alkyl.

90. The compound of claim 89, wherein R4is hydrogen or methyl.

91. The compound of claim 90, wherein R1is .

92. The compound of claim 91, wherein the compound is selected from the group consisting of (2-(1'-(2-acetyl-2-azaspiro[3.3]heptan-6-yl)-5'-fluoro-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (83), (2-(1'-(1-acetylpiperidine-4-carbonyl)-5'-fluoro-1H,1'H-[4,6'- biindazol]-1-yl)acetyl)glycylglycine (84), (2-(1'-(1-acetylpiperidin-4-yl)-5'-fluoro-1H,1'H-[4,6'- biindazol]-1-yl)acetyl)glycylglycine (85), (2-(5'-fluoro-3-methyl-1'-((1-methylpiperidin-4- yl)methyl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (86), and (2-(1'-(2-acetamidoethyl)- 5'-fluoro-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (87).

93. The compound of claim 4, wherein R3, when present, is hydrogen; and R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl.

94. The compound of claim 93, wherein R4, when present, is hydrogen or alkyl.

95. The compound of claim 94, wherein R4is or .

96. The compound of claim 95, wherein R1is .

97. The compound of claim 96, wherein the compound is selected from the group consisting of (2-(3-(1-acetylazetidin-3-yl)-1H-indazol-1-yl)acetyl)glycylglycine (88) and (2-(3-(1- acetylpiperidin-4-yl)-1H-indazol-1-yl)acetyl)glycylglycine (89).

98. The compound of claim 4, wherein is ; R3, when present, is hydrogen; R4, when present, is hydrogen; and R1is .

99. The compound of claim 98, wherein the compound is selected from the group consisting of (2-(1H-indazol-1-yl)acetyl)glycylglycine (90) and methyl (2-(1H-indol-1- yl)acetyl)glycylglycinate (91).

100. The compound of claim 4, wherein is ; R3, when present, is aryl or heteroaryl, wherein aryl or heteroaryl are unsubstituted or substituted with alkyl, heteroalkyl, heterocycloalkyl, and / or halo; and R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl or –C(O)-heteroalkylene-NR4aR4bwherein R4aand R4bare independently hydrogen, alkyl, or acyl.

101. The compound of claim 100, wherein R3is selected from the group consisting of , , , , , , , , , , , and .

102. The compound of claim 101, wherein R4is .

103. The compound of claim 102, wherein R1is .

104. The compound of claim 103, wherein the compound is selected from the group consisting of (2-(3-(1-acetylpiperidin-4-yl)-4-(naphthalen-2-yl)-1H-indazol-1-yl)acetyl)glycylglycine (92), (2-(3-(1-acetylpiperidin-4-yl)-4-(2-fluoro-4-methylphenyl)-1H-indazol-1-yl)acetyl)glycylglycine (93), (2-(3-(1-acetylpiperidin-4-yl)-4-(2,6-difluoro-4-methylphenyl)-1H-indazol-1-yl)acetyl)glycylglycine (94), (2-(3-(1-acetylpiperidin-4-yl)-4-(quinolin-3-yl)-1H-indazol-1- yl)acetyl)glycylglycine (95), (2-(3-(1-acetylpiperidin-4-yl)-4-(quinolin-7-yl)-1H-indazol-1- yl)acetyl)glycylglycine (96), (2-(3-(1-acetylpiperidin-4-yl)-4-(isoquinolin-6-yl)-1H-indazol-1- yl)acetyl)glycylglycine (97), (2-(3-(1-acetylpiperidin-4-yl)-4-(3-methylbenzo[d]isoxazol-6-yl)- 1H-indazol-1-yl)acetyl)glycylglycine (98), (2-(3-(1-acetylpiperidin-4-yl)-4-(benzofuran-2-yl)- 1H-indazol-1-yl)acetyl)glycylglycine (99), (2-(3-(1-acetylpiperidin-4-yl)-4-(benzofuran-6-yl)- 1H-indazol-1-yl)acetyl)glycylglycine (100), (2-(3-(1-acetylpiperidin-4-yl)-4-(benzo[d]isothiazol- 6-yl)-1H-indazol-1-yl)acetyl)glycylglycine (101), (2-(3-(1-acetylpiperidin-4-yl)-4-(isoquinolin- 7-yl)-1H-indazol-1-yl)acetyl)glycylglycine (102), and (2-(3-(1-acetylpiperidin-4-yl)-4-(quinolin- 6-yl)-1H-indazol-1-yl)acetyl)glycylglycine (103).

105. The compound of claim 100, wherein R3is .

106. The compound of claim 105, wherein R4is .

107. The compound of claim 106, wherein R1is .

108. The compound of claim 107, wherein the compound is methyl (2-(3-(1-(3-(2-(2-(2- aminoethoxy)ethoxy)ethoxy)propanoyl)piperidin-4-yl)-4-(5-methyl-6-morpholinopyridin-3-yl)- 1H-indazol-1-yl)acetyl)glycylglycinate (104).

109. The compound of claim 4, wherein is ; R3, when present, is ; and R4, when present, is hydrogen.

110. The compound of claim 109, wherein R3ais alkyl; R3bis hydrogen; and R3cis halo.

111. The compound of claim 110, wherein R3is .

112. The compound of claim 111, wherein R1is .

113. The compound of claim 112, wherein the compound is (2-(4-(5-fluoro-1-methyl-1H- indazol-6-yl)-1H-indol-1-yl)acetyl)glycylglycine (105).

114. The compound of claim 3, wherein is and R3, when present, is .

115. The compound of claim 114, wherein X3is nitrogen and X4is nitrogen.

116. The compound of claim 115, wherein R3ais alkyl; R3bis hydrogen; and R3cis halo.

117. The compound of claim 116, wherein R3is .

118. The compound of claim 117, wherein R1is .

119. The compound of claim 118, wherein the compound is (2-(4-(5-fluoro-1-methyl-1H- indazol-6-yl)-1H-benzo[d]imidazol-1-yl)acetyl)glycylglycine (106).

120. The compound of claim 114, wherein X3is carbon and X4is oxygen.

121. The compound of claim 120, wherein R3ais alkyl; R3bis hydrogen; and R3cis halo.

122. The compound of claim 121, wherein R3is .

123. The compound of claim 122, wherein R1is .

124. The compound of claim 123, wherein the compound is (2-(7-(5-fluoro-1-methyl-1H- indazol-6-yl)benzofuran-3-yl)acetyl)glycylglycine (107).

125. The compound of claim 2, wherein is or and R3, when present, is .

126. The compound of claim 125, wherein R3ais alkyl; R3bis hydrogen; and R3cis halo.

127. The compound of claim 126, wherein R3is .

128. The compound of claim 127, wherein R1is .

129. The compound of claim 128, wherein the compound is selected from the group consisting of (2-(5-(5-fluoro-1-methyl-1H-indazol-6-yl)naphthalen-1-yl)acetyl)glycylglycine (108), (2-(8- (5-fluoro-1-methyl-1H-indazol-6-yl)quinolin-4-yl)acetyl)glycylglycine (219), and (2-(4-(5- fluoro-1-methyl-1H-indazol-6-yl)quinolin-8-yl)acetyl)glycylglycine (109).

130. The compound of claim 3, wherein is ; R3, when present, is ; and R4, when present, is heterocycloalkyl wherein heterocycloalkyl is unsubstituted or substituted with alkyl, alkenyl, alkynyl, heteroalkyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, or –C(O)NR4aR4bwherein R4aand R4bare independently hydrogen or alkyl.

131. The compound of claim 130, wherein R3ais alkyl; R3bis hydrogen; and R3cis halo.

132. The compound of claim 131, wherein R3is .

133. The compound of claim 132, wherein R4, when present, is heterocycloalkyl wherein heterocycloalkyl is unsubstituted or substituted with –C(O)NR4aR4bwherein R4aand R4bare independently hydrogen or alkyl.

134. The compound of claim 133, wherein R4is .

135. The compound of claim 134, wherein R1is .

136. The compound of claim 135, wherein the compound is (2-(5'-fluoro-1'-methyl-3-(4- (methylcarbamoyl)piperidin-1-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (110).

137. The compound of claim 3, wherein is ; R3, when present, is ; and R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl, –C(O)-heteroalkylene-NR4aR4b, alkyl, –C(O)-alkylene-COOR5, –C(O)-alkylene-C(O)NR4aR4b, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl, wherein R4aand R4bare independently hydrogen, alkyl, or acyl.

138. The compound of claim 137, wherein R3ais alkyl; R3bis hydrogen; and R3cis halo.

139. The compound of claim 138, wherein R3is .

140. The compound of claim 139, wherein R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl.

141. The compound of claim 140, wherein R4is .

142. The compound of claim 141, wherein R1is .

143. The compound of claim 142, wherein the compound is selected from the group consisting of (2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)ethyl)glycylglycine (111), (2-(2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-1-yl)acetamido)ethyl)glycine (112), and (5-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'- methyl-1H,1'H-[4,6'-biindazol]-1-yl)pentanoyl)glycine (113).

144. The compound of claim 3, wherein is ; R3, when present, is heteroaryl wherein heteroaryl is unsubstituted or substituted with alkyl, heteroalkyl, heterocycloalkyl, and / or halo; R4, when present, is hydrogen; and R1is .

145. The compound of claim 144, wherein the compound is (2-(4-(4-fluoro-1-methyl-1H- pyrazol-5-yl)-1H-indazol-1-yl)acetyl)glycylglycine (114) or (2-(4-(1-methyl-1H-pyrazol-5-yl)- 1H-indazol-1-yl)acetyl)glycylglycine (115).

146. The compound of claim 3, wherein is ; R3, when present, is ; and R4, when present, is hydrogen.

147. The compound of claim 146, wherein R3ais alkyl; R3bis hydrogen; and R3cis halo.

148. The compound of claim 147, wherein R3is .

149. The compound of claim 148, wherein R1is .

150. The compound of claim 149, wherein the compound is selected from the group consisting of (2-(5'-fluoro-7-hydroxy-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (116), (2- (5'-fluoro-1'-methyl-7-(trifluoromethoxy)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (117), (2-(5'-fluoro-1',7-dimethyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (118), (2-(5'- fluoro-7-methoxy-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (119), (2-(5'- fluoro-1',6-dimethyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (120), and (2-(5'-fluoro- 1',5-dimethyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (121).

151. The compound of claim 2, having the following formulaor a pharmaceutically acceptable salt thereof, wherein one of R3ais hydrogen or C1-5alkyl; R5is hydrogen or C1-5alkyl; R9is ; each R9ais independently hydrogen or alkyl; R9bis -C(O)OR9cor ; each R9cis hydrogen or C1-5alkyl; bb is one or two; and R3cis hydrogen, halogen, or CN.

152. The compound of claim 151, wherein each R9ais hydrogen.

153. The compound of claim 151 or 152, wherein R9cis hydrogen or methyl.

154. The compound of any one of claims 151-153, wherein bb is one.

155. The compound of any one of claims 151-153, wherein bb is two.

156. The compound of claim 2, wherein R3ais –C(O)-alkylene-C(O)R3aaawherein R3aaais –OR7a, –NR7aR7bor alkyl; R3bis hydrogen; and R3cis fluoro.

157. The compound of claim 156, having the following formula.

158. The compound of claim 156, wherein R3is , , or .

159. The compound of any one of claims 156-158, wherein R4, when present, is hydrogen or alkyl.

160. The compound of any one of claims 156-159, wherein R4is hydrogen, methyl, or isopropyl.

161. The compound of any one of claims 156-160, wherein R1is .

162. The compound of any one of claims 156-161, wherein the compound is selected from the group consisting of 4-(1-(2-((2-((carboxymethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-5'- fluoro-3-methyl-1H,1'H-[4,6'-biindazol]-1'-yl)-4-oxobutanoic acid (122), 4-(5'-fluoro-1-(2-((2- ((2-methoxy-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-3-methyl-1H,1'H-[4,6'- biindazol]-1'-yl)-4-oxobutanoic acid (123), 4-(1-(2-((2-((2-(tert-butoxy)-2-oxoethyl)amino)-2- oxoethyl)amino)-2-oxoethyl)-5'-fluoro-3-methyl-1H,1'H-[4,6'-biindazol]-1'-yl)-4-oxobutanoicacid (124), (2-(1'-(4-amino-4-oxobutanoyl)-5'-fluoro-3-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (125), methyl (2-(1'-(4-amino-4-oxobutanoyl)-5'-fluoro-3-methyl- 1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (126), tert-butyl (2-(1'-(4-amino-4- oxobutanoyl)-5'-fluoro-3-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (127), (2- (5'-fluoro-3-methyl-1'-(4-oxopentanoyl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (128), methyl (2-(5'-fluoro-3-methyl-1'-(4-oxopentanoyl)-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (129), tert-butyl (2-(5'-fluoro-3-methyl-1'-(4-oxopentanoyl)-1H,1'H- [4,6'-biindazol]-1-yl)acetyl)glycylglycinate (130), 4-(1-(2-((2-((carboxymethyl)amino)-2- oxoethyl)amino)-2-oxoethyl)-5'-fluoro-3-isopropyl-1H,1'H-[4,6'-biindazol]-1'-yl)-4-oxobutanoic acid (131), 4-(5'-fluoro-3-isopropyl-1-(2-((2-((2-methoxy-2-oxoethyl)amino)-2-oxoethyl)amino)- 2-oxoethyl)-1H,1'H-[4,6'-biindazol]-1'-yl)-4-oxobutanoic acid (132), 4-(1-(2-((2-((2-(tert- butoxy)-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-5'-fluoro-3-isopropyl-1H,1'H-[4,6'- biindazol]-1'-yl)-4-oxobutanoic acid (133), (2-(1'-(4-amino-4-oxobutanoyl)-5'-fluoro-3- isopropyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (134), methyl (2-(1'-(4-amino-4- oxobutanoyl)-5'-fluoro-3-isopropyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (135), tert-butyl (2-(1'-(4-amino-4-oxobutanoyl)-5'-fluoro-3-isopropyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (136), (2-(5'-fluoro-3-isopropyl-1'-(4-oxopentanoyl)-1H,1'H-[4,6'- biindazol]-1-yl)acetyl)glycylglycine (137), methyl (2-(5'-fluoro-3-isopropyl-1'-(4-oxopentanoyl)- 1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (138), and tert-butyl (2-(5'-fluoro-3- isopropyl-1'-(4-oxopentanoyl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (139).

163. The compound of claim 2, R3is , , , or .

164. The compound of claim 163, wherein R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is substituted with –C(O)-alkylene-C(O)R3aaawherein R3aaais –OR7a, –NR7aR7bor alkyl; or alkyl.

165. The compound of claim 163 or 164, having the following formulawherein R4aais –C(O)-alkylene-C(O)R3aaawherein R3aaais –OR7a, –NR7aR7bor alkyl; or alkyl.

166. The compound of any one of claims 163-165, wherein R4aais methyl, , , or .

167. The compound of any one of claims 163-165, selected from the group consisting of 2-(4- ((2-(5'-fluoro-1'-methyl-3-(1-methylpiperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1- yl)acetamido)methyl)-1H-1,2,3-triazol-1-yl)acetic acid (140), methyl 2-(4-((2-(5'-fluoro-1'- methyl-3-(1-methylpiperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)methyl)-1H-1,2,3- triazol-1-yl)acetate (141), tert-butyl 2-(4-((2-(5'-fluoro-1'-methyl-3-(1-methylpiperidin-4-yl)- 1H,1'H-[4,6'-biindazol]-1-yl)acetamido)methyl)-1H-1,2,3-triazol-1-yl)acetate (142), 4-(4-(1-(2- (((1-(carboxymethyl)-1H-1,2,3-triazol-4-yl)methyl)amino)-2-oxoethyl)-5'-fluoro-1'-methyl- 1H,1'H-[4,6'-biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid (143), 4-(4-(5'-fluoro-1-(2-(((1- (2-methoxy-2-oxoethyl)-1H-1,2,3-triazol-4-yl)methyl)amino)-2-oxoethyl)-1'-methyl-1H,1'H- [4,6'-biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid (144), 4-(4-(1-(2-(((1-(2-(tert-butoxy)-2- oxoethyl)-1H-1,2,3-triazol-4-yl)methyl)amino)-2-oxoethyl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid (145), 2-(4-((2-(3-(1-(4-amino-4- oxobutanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)methyl)- 1H-1,2,3-triazol-1-yl)acetic acid (146), methyl 2-(4-((2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)methyl)-1H-1,2,3-triazol-1- yl)acetate (147), tert-butyl 2-(4-((2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-5'-fluoro-1'- methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)methyl)-1H-1,2,3-triazol-1-yl)acetate (148), 2- (4-((2-(5'-fluoro-1'-methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1- yl)acetamido)methyl)-1H-1,2,3-triazol-1-yl)acetic acid (149), methyl 2-(4-((2-(5'-fluoro-1'- methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)methyl)- 1H-1,2,3-triazol-1-yl)acetate (150), and tert-butyl 2-(4-((2-(5'-fluoro-1'-methyl-3-(1-(4- oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)methyl)-1H-1,2,3-triazol- 1-yl)acetate (151).

168. The compound of claim 2, wherein R4, when present, is a five- to fifteen-membered spiro bicyclic heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, or –C(O)-alkylene-C(O)R3aaawherein R3aaais –OR7a, –NR7aR7bor alkyl.

169. The compound of claim 168, having the following formula wherein R3bis alkyl and R3cis halo.

170. The compound of claim 168 or 169, selected from the group consisting of 4-(6-(1-(2-((2- ((carboxymethyl)amino)-2-oxoethyl)(methyl)amino)-2-oxoethyl)-5'-fluoro-1'-methyl-1H,1'H- [4,6'-biindazol]-3-yl)-2-azaspiro[3.3]heptan-2-yl)-4-oxobutanoic acid (152), 4-(6-(5'-fluoro-1-(2- ((2-((2-methoxy-2-oxoethyl)amino)-2-oxoethyl)(methyl)amino)-2-oxoethyl)-1'-methyl-1H,1'H- [4,6'-biindazol]-3-yl)-2-azaspiro[3.3]heptan-2-yl)-4-oxobutanoic acid (153), 4-(6-(1-(2-((2-((2- (tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)(methyl)amino)-2-oxoethyl)-5'-fluoro-1'-methyl- 1H,1'H-[4,6'-biindazol]-3-yl)-2-azaspiro[3.3]heptan-2-yl)-4-oxobutanoic acid (154), N-(2-(3-(2- (4-amino-4-oxobutanoyl)-2-azaspiro[3.3]heptan-6-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N-methylglycylglycine (155), methyl N-(2-(3-(2-(4-amino-4- oxobutanoyl)-2-azaspiro[3.3]heptan-6-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)-N-methylglycylglycinate (156), tert-butyl N-(2-(3-(2-(4-amino-4-oxobutanoyl)-2- azaspiro[3.3]heptan-6-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N- methylglycylglycinate (157), N-(2-(5'-fluoro-1'-methyl-3-(2-(4-oxopentanoyl)-2- azaspiro[3.3]heptan-6-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N-methylglycylglycine (158), methyl N-(2-(5'-fluoro-1'-methyl-3-(2-(4-oxopentanoyl)-2-azaspiro[3.3]heptan-6-yl)-1H,1'H- [4,6'-biindazol]-1-yl)acetyl)-N-methylglycylglycinate (159), and tert-butyl N-(2-(5'-fluoro-1'- methyl-3-(2-(4-oxopentanoyl)-2-azaspiro[3.3]heptan-6-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)- N-methylglycylglycinate (160).

171. The compound of claim 2, wherein R3is , , , , or .

172. The compound of claim 171, wherein R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with –C(O)-alkylene-C(O)R3aaawherein R3aaais –OR7a, –NR7aR7bor alkyl.

173. The compound of claim 171 or 172, wherein R1is .

174. The compound of any one of claims 171-173, wherein the formula of the compound is selected from the group consisting of , , , , and .

175. The compound of any one of claims 171-174, selected from the group consisting of 4-(4- (1-(2-((2-((carboxymethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-5'-fluoro-1'-methyl-1H,1'H- [4,6'-biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid (161), 4-(4-(5'-fluoro-1-(2-((2-((2- methoxy-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-1'-methyl-1H,1'H-[4,6'-biindazol]- 3-yl)piperidin-1-yl)-4-oxobutanoic acid (162), 4-(4-(1-(2-((2-((2-(tert-butoxy)-2- oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-3- yl)piperidin-1-yl)-4-oxobutanoic acid (163), (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-5'- fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (164), methyl (2-(3-(1-(4- amino-4-oxobutanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (165), tert-butyl (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (166), (2-(5'-fluoro-1'- methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (167), methyl (2-(5'-fluoro-1'-methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'- biindazol]-1-yl)acetyl)glycylglycinate (168), tert-butyl (2-(5'-fluoro-1'-methyl-3-(1-(4- oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (169), 4-(4-(1- (2-((2-((carboxymethyl)amino)-2-oxoethyl)(methyl)amino)-2-oxoethyl)-5'-fluoro-1'-methyl- 1H,1'H-[4,6'-biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid (170), 4-(4-(5'-fluoro-1-(2-((2- ((2-methoxy-2-oxoethyl)amino)-2-oxoethyl)(methyl)amino)-2-oxoethyl)-1'-methyl-1H,1'H-[4,6'- biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid (171), 4-(4-(1-(2-((2-((2-(tert-butoxy)-2- oxoethyl)amino)-2-oxoethyl)(methyl)amino)-2-oxoethyl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'- biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid (172), N-(2-(3-(1-(4-amino-4- oxobutanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N- methylglycylglycine (173), methyl N-(2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-5'-fluoro- 1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N-methylglycylglycinate (174), tert-butyl N-(2- (3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)-N-methylglycylglycinate (175), N-(2-(5'-fluoro-1'-methyl-3-(1-(4- oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N-methylglycylglycine (176), methyl N-(2-(5'-fluoro-1'-methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]- 1-yl)acetyl)-N-methylglycylglycinate (177), tert-butyl N-(2-(5'-fluoro-1'-methyl-3-(1-(4- oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N-methylglycylglycinate (178), 4-(4-(1-(2-((2-((carboxymethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-1'-methyl-1H,1'H- [4,6'-biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid (179), 4-(4-(1-(2-((2-((2-methoxy-2- oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-1'-methyl-1H,1'H-[4,6'-biindazol]-3- yl)piperidin-1-yl)-4-oxobutanoic acid (180), 4-(4-(1-(2-((2-((2-(tert-butoxy)-2-oxoethyl)amino)- 2-oxoethyl)amino)-2-oxoethyl)-1'-methyl-1H,1'H-[4,6'-biindazol]-3-yl)piperidin-1-yl)-4- oxobutanoic acid (181), (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-1'-methyl-1H,1'H- [4,6'-biindazol]-1-yl)acetyl)glycylglycine (182), methyl (2-(3-(1-(4-amino-4- oxobutanoyl)piperidin-4-yl)-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (183), tert-butyl (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (184), (2-(1'-methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'- biindazol]-1-yl)acetyl)glycylglycine (185), methyl (2-(1'-methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (186), tert-butyl (2-(1'-methyl-3-(1-(4- oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (187), 4-(4-(1- (2-((2-((carboxymethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-4-(5-fluoro-1-methyl-1H- indazol-6-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)piperidin-1-yl)-4-oxobutanoic acid (188), 4-(4-(4- (5-fluoro-1-methyl-1H-indazol-6-yl)-1-(2-((2-((2-methoxy-2-oxoethyl)amino)-2- oxoethyl)amino)-2-oxoethyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)piperidin-1-yl)-4-oxobutanoic acid (189), 4-(4-(1-(2-((2-((2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-4-(5- fluoro-1-methyl-1H-indazol-6-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl)piperidin-1-yl)-4-oxobutanoic acid (190), (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-4-(5-fluoro-1-methyl-1H-indazol-6- yl)-1H-pyrazolo[3,4-b]pyridin-1-yl)acetyl)glycylglycine (191), methyl (2-(3-(1-(4-amino-4- oxobutanoyl)piperidin-4-yl)-4-(5-fluoro-1-methyl-1H-indazol-6-yl)-1H-pyrazolo[3,4-b]pyridin- 1-yl)acetyl)glycylglycinate (192), tert-butyl (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-4- (5-fluoro-1-methyl-1H-indazol-6-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl)acetyl)glycylglycinate (193), (2-(4-(5-fluoro-1-methyl-1H-indazol-6-yl)-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H- pyrazolo[3,4-b]pyridin-1-yl)acetyl)glycylglycine (194), methyl (2-(4-(5-fluoro-1-methyl-1H- indazol-6-yl)-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H-pyrazolo[3,4-b]pyridin-1- yl)acetyl)glycylglycinate (195), tert-butyl (2-(4-(5-fluoro-1-methyl-1H-indazol-6-yl)-3-(1-(4- oxopentanoyl)piperidin-4-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl)acetyl)glycylglycinate (196), 4-(4- (1-(2-((2-((carboxymethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-7'-fluoro-1'-methyl-1H,1'H- [4,6'-biindazol]-3-yl)piperidin-1-yl)-4-oxobutanoic acid (197), 4-(4-(7'-fluoro-1-(2-((2-((2- methoxy-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-1'-methyl-1H,1'H-[4,6'-biindazol]- 3-yl)piperidin-1-yl)-4-oxobutanoic acid (198), 4-(4-(1-(2-((2-((2-(tert-butoxy)-2- oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-7'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-3- yl)piperidin-1-yl)-4-oxobutanoic acid (199), (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-7'- fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (200), methyl (2-(3-(1-(4- amino-4-oxobutanoyl)piperidin-4-yl)-7'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (201), tert-butyl (2-(3-(1-(4-amino-4-oxobutanoyl)piperidin-4-yl)-7'- fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (202), (2-(7'-fluoro-1'- methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (203), methyl (2-(7'-fluoro-1'-methyl-3-(1-(4-oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (204), and tert-butyl (2-(7'-fluoro-1'-methyl-3-(1-(4- oxopentanoyl)piperidin-4-yl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (205).

176. The compound of claim 2, wherein R3ais –C(O)-(three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, or – C(O)-alkylene-C(O)R3aaawherein R3aaais –OR7a, –NR7aR7bor alkyl); R3bis hydrogen; and R3cis fluoro.

177. The compound of claim 176, wherein R4, when present, is hydrogen or alkyl.

178. The compound of claim 176 or 177, wherein R1is .

179. The compound of any one of claims 176-178, having the following formula .

180. The compound of any one of claims 176-179, selected from the group consisting of 4-(4- (1-(2-((2-((carboxymethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-5'-fluoro-1H,1'H-[4,6'- biindazole]-1'-carbonyl)piperidin-1-yl)-4-oxobutanoic acid (206), 4-(4-(5'-fluoro-1-(2-((2-((2- methoxy-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-1H,1'H-[4,6'-biindazole]-1'- carbonyl)piperidin-1-yl)-4-oxobutanoic acid (207), 4-(4-(1-(2-((2-((2-(tert-butoxy)-2- oxoethyl)amino)-2-oxoethyl)amino)-2-oxoethyl)-5'-fluoro-1H,1'H-[4,6'-biindazole]-1'- carbonyl)piperidin-1-yl)-4-oxobutanoic acid (208), (2-(1'-(1-(4-amino-4-oxobutanoyl)piperidine- 4-carbonyl)-5'-fluoro-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (209), methyl (2-(1'-(1- (4-amino-4-oxobutanoyl)piperidine-4-carbonyl)-5'-fluoro-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (210), tert-butyl (2-(1'-(1-(4-amino-4-oxobutanoyl)piperidine-4- carbonyl)-5'-fluoro-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (211), (2-(5'-fluoro-1'-(1-(4-oxopentanoyl)piperidine-4-carbonyl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (212), methyl (2-(5'-fluoro-1'-(1-(4-oxopentanoyl)piperidine-4-carbonyl)-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (213), and tert-butyl (2-(5'-fluoro-1'-(1-(4-oxopentanoyl)piperidine-4- carbonyl)-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycinate (214).

181. The compound of claim 2, wherein is ; R3, when present, is ; and R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl, –C(O)-heteroalkylene-NR4aR4b, alkyl, –C(O)-alkylene-COOR5, –C(O)-alkylene-C(O)NR4aR4b, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl, wherein R4aand R4bare independently hydrogen, alkyl, or acyl.

182. The compound of claim 181, wherein R3ais alkyl; R3bis hydrogen; and R3cis one or more alkoxy or halo.

183. The compound of claim 182, wherein R3is , , , , or .

184. The compound of claim 183, wherein R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl.

185. The compound of claim 184, wherein R4is , , , , or .

186. The compound of claim 185, wherein R1is and R9is , or .

187. The compound of claim 186, wherein R9is , , or .

188. The compound of claim 187, wherein the compound is selected from the group consisting of 3-((2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetamido)methyl)-4-fluorobenzoic acid (220), 2-(2-((2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro- 1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)methyl)thiazol-4-yl)acetic acid (221), 2-(4-((2- (3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetamido)methyl)- 1H-1,2,3-triazol-1-yl)acetic acid (222), and 2-(4-((2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'- methyl-1H,1'H-[4,6'-biindazol]-1-yl)-N-methylacetamido)methyl)-1H-1,2,3-triazol-1-yl)acetic acid (226).

189. The compound of claim 2, wherein is ; R3, when present, is ; and R4, when present, is hydrogen or a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl, –C(O)-heteroalkylene-NR4aR4b, alkyl, –C(O)-alkylene- COOR5, –C(O)-alkylene-C(O)NR4aR4b, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl, wherein R4aand R4bare independently hydrogen, alkyl, or acyl.

190. The compound of claim 189, wherein R3ais alkyl; R3bis hydrogen; and R3cis one or more alkoxy or halo.

191. The compound of claim 190, wherein R3is , , , , or .

192. The compound of claim 191, wherein R4, when present, is hydrogen or a three- to eight- membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl.

193. The compound of claim 192, wherein R4is hydrogen, , , , , or .

194. The compound of claim 193, wherein R1is .

195. The compound of claim 194, wherein the compound is selected from the group consisting of (2-(3-(1-acetylpiperidin-4-yl)-7-amino-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (223) and (2-(5'-fluoro-1'-methyl-7-(methylthio)-1H,1'H-[4,6'-biindazol]- 1-yl)acetyl)glycylglycine (224).

196. The compound of claim 2, wherein is ; R3, when present, is or ; and R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl, –C(O)-heteroalkylene-NR4aR4b, alkyl, –C(O)-alkylene-COOR5, –C(O)-alkylene-C(O)NR4aR4b,heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl, wherein R4aand R4bare independently hydrogen, alkyl, or acyl; or a five- to fifteen-membered spiro bicyclic heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, or –C(O)-alkylene-C(O)R3aaawherein R3aaais –OR7a, –NR7aR7bor alkyl.

197. The compound of claim 196, wherein R3ais alkyl; R3bis hydrogen; and R3cis one or more alkoxy, cyano, or halo.

198. The compound of claim 197, wherein R3is , , , , , or .

199. The compound of claim 198, wherein R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen; or a five- to fifteen-membered spiro bicyclic heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl.

200. The compound of claim 199, wherein R4is , , , , , or .

201. The compound of claim 200, wherein R1is .

202. The compound of claim 201, wherein the compound is selected from the group consisting of N-(2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N- cyclopropylglycylglycine (225), N-(2-(3-(1-acetylpiperidin-4-yl)-5'-fluoro-2'-methyl-1H,2'H- [4,6'-biindazol]-1-yl)acetyl)-N-cyclopropylglycylglycine (227), and N-(2-(3-(2-acetyl-2- azaspiro[3.3]heptan-6-yl)-5'-cyano-1'-methyl-1H,1'H-[4,6'-biindazol]-1-yl)acetyl)-N- methylglycylglycine (228).

203. The compound of claim 3, wherein is ; R3, when present, is aryl or heteroaryl, wherein aryl or heteroaryl are unsubstituted or substituted with alkyl, heteroalkyl, heterocycloalkyl, and / or halo; and R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl, –C(O)-heteroalkylene-NR4aR4b, alkyl, –C(O)-alkylene-COOR5, –C(O)-alkylene-C(O)NR4aR4b, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl, wherein R4aand R4bare independently hydrogen, alkyl, or acyl.

204. The compound of claim 203, wherein R3is or .

205. The compound of claim 204, wherein R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl.

206. The compound of claim 205, wherein R4is , , , , or .

207. The compound of claim 206, wherein R1is .

208. The compound of claim 207, wherein the compound is selected from the group consisting of (2-(3-(1-acetylpiperidin-4-yl)-4-(isoquinolin-3-yl)-1H-indazol-1-yl)acetyl)glycylglycine (230) and (2-(3-(1-acetylpiperidin-4-yl)-4-(1-methyl-1H-indol-6-yl)-1H-indazol-1- yl)acetyl)glycylglycine (231).

209. The compound of claim 2, wherein is ; R3, when present, is ; and R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with acyl, –C(O)-heteroalkylene-NR4aR4b, alkyl, –C(O)-alkylene-COOR5, –C(O)-alkylene- C(O)NR4aR4b, –C(O)-alkylene-C(O)N(R4a)-heteroalkylene-halo, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, or heteroaryl, wherein R4aand R4bare independently hydrogen, alkyl, or acyl.

210. The compound of claim 209, wherein R3ais alkyl; R3bis hydrogen; and R3cis one or more alkoxy or halo.

211. The compound of claim 210, wherein R3is , , , , or .

212. The compound of claim 211, wherein R4, when present, is a three- to eight-membered heterocycloalkyl comprising at least one nitrogen, wherein the at least one nitrogen is unsubstituted or substituted with –C(O)-alkylene-C(O)N(R4a)-heteroalkylene-halo wherein R4ais hydrogen, alkyl, or acyl.

213. The compound of claim 212, wherein R4is selected from the group consisting of , , , and .

214. The compound of claim 213, wherein R1is .

215. The compound of claim 214, wherein the compound is selected from the group consisting of (2-(3-(1-(20-chloro-4-oxo-8,11,14-trioxa-5-azaicosanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl- 1H,1'H-[4,6'-biindazol]-1-yl)acetyl)glycylglycine (232), methyl (2-(3-(1-(20-chloro-4-oxo- 8,11,14-trioxa-5-azaicosanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (233), (2-(3-(1-(23-chloro-4-oxo-8,11,14,17-tetraoxa-5- azatricosanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (234), methyl (2-(3-(1-(23-chloro-4-oxo-8,11,14,17-tetraoxa-5- azatricosanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (235), (2-(3-(1-(26-chloro-4-oxo-8,11,14,17,20-pentaoxa-5- azahexacosanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (236), methyl (2-(3-(1-(26-chloro-4-oxo-8,11,14,17,20-pentaoxa-5- azahexacosanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (237), (2-(3-(1-(29-chloro-4-oxo-8,11,14,17,20,23-hexaoxa-5- azanonacosanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycine (238), and methyl (2-(3-(1-(29-chloro-4-oxo-8,11,14,17,20,23-hexaoxa- 5-azanonacosanoyl)piperidin-4-yl)-5'-fluoro-1'-methyl-1H,1'H-[4,6'-biindazol]-1- yl)acetyl)glycylglycinate (239).

216. A compound having the following formula or a pharmaceutically acceptable salt thereof, wherein each is independently arylene or heteroarylene wherein arylene or heteroarylene are unsubstituted or substituted with one or more alkyl, heteroalkyl, alkenyl, alkynyl, acyl,cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, halo, heteroaryl, or –C(O)NR1R2, wherein R1and R2are independently hydrogen or alkyl; is cycloalkylene or heterocycloalkylene wherein cycloalkylene or heterocycloalkylene are unsubstituted or substituted with one or more alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, halo, heteroaryl, or –C(O)NR1R2, wherein R1and R2are independently hydrogen or alkyl; each X1is -N(R3)-, oxygen, or sulfur wherein R3is hydrogen or alkyl; X2is N(R4), oxygen, or sulfur, wherein R4is hydrogen or alkyl; and each n is an integer from one to five.

217. The compound claim 216, selected from the group consisting of (S)-5-(2-fluoro-6-hydroxypyridin-3-yl)-N-methyl-2-((1-(3-((1-methyl-1H-tetrazol-5- yl)methoxy)benzoyl)piperidin-3-yl)methoxy)benzamide (240), (R)-5-(2-fluoro-6- hydroxypyridin-3-yl)-N-methyl-2-((1-(3-((1-methyl-1H-tetrazol-5- yl)methoxy)benzoyl)piperidin-3-yl)methoxy)benzamide (241), (S)-5-(2-fluoro-6- hydroxypyridin-3-yl)-N-methyl-2-((4-(3-((1-methyl-1H-tetrazol-5- yl)methoxy)benzoyl)morpholin-2-yl)methoxy)benzamide (242), and (R)-5-(2-fluoro-6- hydroxypyridin-3-yl)-N-methyl-2-((4-(3-((1-methyl-1H-tetrazol-5- yl)methoxy)benzoyl)morpholin-2-yl)methoxy)benzamide (243).

218. A compound having the following formula or a pharmaceutically acceptable salt thereof, wherein is cycloalkylene or heterocycloalkylene wherein cycloalkylene or heterocycloalkylene are unsubstituted or substituted with one or more alkyl, heteroalkyl, alkenyl,alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, halo, heteroaryl, or –C(O)NRaRb, wherein Raand Rbare independently hydrogen or alkyl; is arylene or heteroarylene wherein arylene or heteroarylene are unsubstituted or substituted with one or more alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, halo, heteroaryl, or –C(O)NRaRb, wherein Raand Rbare independently hydrogen or alkyl; each R1is independently hydrogen or alkyl; R2is hydrogen or alkyl; and each n is independently an integer from one to eight.

219. The compound of claim 218, wherein the compound is N-(2-(2-(2-(2- aminoethoxy)ethoxy)ethoxy)ethyl)-6-(4-(2-(1-(2-(3,5- dioxomorpholino)acetamido)cyclobutyl)acetamido)piperidin-1-yl)nicotinamide (244).

220. A compound having the following formula or a pharmaceutically acceptable salt thereof, wherein and are independently arylene or heteroarylene wherein arylene or heteroarylene are unsubstituted or substituted with one or more alkyl, heteroalkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, halo, heteroaryl, or –C(O)NRaRb, wherein Raand Rbare independently hydrogen or alkyl; each R1is independently hydrogen or alkyl; R2is hydrogen or alkyl; and each n is independently an integer from one to eight.

221. The compound of claim 220, wherein the compound is N-(2-(2-(2-(2- aminoethoxy)ethoxy)ethoxy)ethyl)-5-((2-(3,5-dioxomorpholino)-N-(imidazo[2,1-b]thiazol-3- ylmethyl)acetamido)methyl)-2,4-dimethylbenzamide (245).

222. A pharmaceutical composition comprising the compound of any one of the previous claims and a pharmaceutically acceptable carrier, excipient, and / or diluent.

223. A method of treating a disease or disorder in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the compound or composition of any one of the previous claims.

224. The method of claim 222, wherein the disease or disorder is cancer.

225. The compound or composition of any one of the previous claims for use in therapy.

226. The compound or composition of any one of the previous claims for use in the treatment of cancer.