BRD9 Inhibitor

BI-7273 is a selective, and cell-permeable BRD9 inhibitor, with an IC₅₀ and a K_d of 19 and 0.75 nM; also shows high effect on BRD7, with an IC₅₀ and a K_d of 117 nM and 0.3 nM.

CFT8634 is an orally active BRD9 PROTAC degrader with a DC₅₀ of 0.003 μM (HEK293T.166). CFT8634 recruits the CRBN E3 ubiquitin ligase to form a ternary complex, triggering CRBN-catalyzed BRD9 polyubiquitination and 26S proteasome-mediated degradation. CFT8634 induces sustained tumor regression and inhibits tumor growth in mouse models. CFT8634 can be used in research related to synovial sarcoma, SMARCB-1-deficient cancers, acute myeloid leukemia, malignant rhabdoid tumors, and multiple myeloma.

VZ185 is a BRD9 and BRD7 PROTAC degrader, with DC₅₀ values of 1.76 nM and 4.5 nM, respectively, in RI-1 cells; and DC₅₀ values of 4 nM and 34 nM, respectively, in HEK293 cells. VZ185 hijacks the CRL2^VHL E3 ubiquitin ligase complex to induce ubiquitination and subsequent proteasomal degradation of BRD9 and BRD7. VZ185 can be used in research related to acute myeloid eosinophilic leukemia and malignant rhabdoid tumors.

BI-9564, a chemical probe, is a potent, selective and cell-permeable BRD9/BRD7 bromodomains inhibitor, with IC₅₀s of 75 nM and 3.4 μM and K_ds of 14 nM and 239 nM, respectively. BI-9564 has an IC₅₀ of > 100 μM for BET family.

NVS-CECR2-1, a non-BET family Bromodomain (BRD) inhibitor, is a potent and selective cat eye syndrome chromosome region, candidate 2 (CECR2) inhibitor. NVS-CECR2-1 binds to CECR2 BRD with high affinity (IC₅₀=47 nM; K_D=80 nM). NVS-CECR2-1 exhibits cytotoxic activity and induces apoptosis against various cancer cells by targeting CECR2 as well as via CECR2-independent mechanism. NVS-CECR2-1 is a chemical probe.

TP-472, a chemical probe, is a selective BRD9/7 inhibitor, with K_ds of 33 nM and 340 nM for BRD9 and BRD7, respectively. TP-472 exhibits >30-fold selectivity for BRD9 over other bromodomain family members except BRD7. TP-472 induces apoptosis of melanoma cells.

BRD7-IN-2 (compound 2-77) is a potent inhibitor of bromodomain-containing protein 7 (BRD7), targeting to prostate cancer cells. BRD7-IN-2 is selective for BRD7 rather than BRD9, with IC50s of 5.4 μM, and >300 μM, respectively.

PROTAC BRD9 Degrader-1 is a PROTAC connected by ligands for Cereblon and BRD9 (IC₅₀=13.5 nM), which can be used as a selective probe useful for the study of BAF complex biology.

GNE-375 is a potent and highly selective BRD9 inhibitor with an IC₅₀ of 5 nM. GNE-375 shows >100-fold selective for BRD9 over BRD4, TAF1, and CECR2. GNE-375 decreases BRD9 binding to chromatin.

NI-42 (compound 13-d), a structurally orthogonal chemical probe for the BRPFs, is a biased, potent inhibitor of the BRD of the BRPFs (IC₅₀s of BRPF1/2/3=7.9/48/260 nM; K_ds of BRPF1/2/3=40/210/940 nM) with excellent selectivity over nonclass IV BRD proteins.

TP-238 hydrochloride is a potent and selective dual CECR2/BPTF probe with IC₅₀ values of 30 nM and 350 nM, respectively. TP-238 hydrochloride also inhibits BRD9 with a pIC₅₀ of 5.9 and is less active against other 338 kinases.

(2S,3R)-LP99 is a potent and selective BRD7 and BRD9 inhibitor with an K_D of 99 nM for BRD9. (2S,3R)-LP99 inhibits the association of BRD7 and BRD9 to acetylated histones in vitro and in cells. (2S,3R)-LP99 demonstrates that BRD7/9 plays a role in regulating pro-inflammatory cytokine secretion.

BRD7-IN-1 free base, a modified derivative of BI7273 (BRD7/9 inhibitor), binds to a VHL ligand via a linker to form a PROTAC VZ185 (VZ185 against BRD7/9 with DC₅₀s of 4.5 and 1.8 nM, respectively).

BRD9 ligand-5 (Compound 172-11) is a PROTAC target protein ligand (Ligands for Target Protein for PROTACs). BRD9 ligand-5 can be utilized for the synthesis of CFT8634 (HY-145925B).

BD-IN-1 is a pan bromodomain (BD) inhibitor with K_D values of 250, 420, 130, 430, 67, 240, 970 nM for BRD4(1), CBP, BRPF1B, BRD7, BRD9, BRDT(1), CECR2 respectively. BD-IN-1 shows antiproliferative activity.

QA-68 (QA-68-ZU81) is an effective PROTAC-class BRD9 degrader. QA-68 can inhibit cell cycle progression and cell colony formation. QA-68 has antiproliferative activity against acute myeloid leukemia (AML) cell lines

TP-238 is a potent and selective dual CECR2/BPTF probe with IC₅₀ values of 30 nM and 350 nM, respectively. TP-238 also inhibits BRD9 with a pIC₅₀ of 5.9 and is less active against other 338 kinases.

(S,R)-CFT8634 is a BRD9 PROTAC degrader that exerts activity via the ubiquitin-proteasome pathway. (S,R)-CFT8634 can be used in the research of acute myeloid leukemia, malignant rhabdoid tumor, synovial sarcoma, and multiple myeloma.