BRD3 Inhibitor

XD14 is a potent BET inhibitor with antitumor effect. It binds to BRD2, BRD3, and BRD4 with K_ds of 170, 380, and 160 nM, respectively.

XY221 (Compound 16o) selectively inhibits BRD4 BD2, with an IC₅₀ of 5.8 nM. XY221 demonstrates high pan-BD2 selectivity (667-fold over BRD4 BD1) and BRD4 BD2 domain selectivity (9−32-fold over BRD2/3/T BD2). XY221 induce Apoptosis in MV4-11 cells and shows anticancer activity .

BY27 is a potent and selective BET BD2 inhibitor, shows 38, 5, 7, and 21-fold BD1/BD2 selectivity for BRD2, BRD3, BRD4, and BRDT. Anti-cancer activity.

BET-IN-30 (Compound 11d) is a BTE family protein inhibitor, which can act as a BRD2/BRD3/BRD4 target protein ligand and be used for the synthesis of PROTACs, such as PROTAC BET Degrader-15 (HY-181729). BET-IN-30 exhibits potent anti-proliferative activity against acute myeloid leukemia (AML) cells such as MV4-11. BET-IN-30 can be used for the study of AML.

SJ46421 is a BRD3BD2 PROTAC degrader. SJ46421 induces a cooperative ternary complex of KLHDC2 and BRD3BD2 with an IC₅₀ of 7.8 nM. SJ46421 binds to the substrate-binding pocket of KLHDC2, forms cooperative ternary complexes with BRD3BD2, BRD2BD2 and BRD4BD2, disrupts the autoinhibitory tetramer assembly of KLHDC2, drives selective ubiquitination of BRD3BD2, and inhibits the ubiquitination of endogenous KLHDC2 diglycine substrates. SJ46421 can be used in cancer research.

BET-IN-13 is a potent BET inhibitor with an IC₅₀ value of 1.6 nM. BET-IN-13 reduces LPS-induced TNF-α, IL-1β, IL-6, and NOS2 mRNA expression levels. BET-IN-13 shows anti-inflammatory activity. BET-IN-13 has the potential for the research of acute liver injury.

BET BD2-IN-1 (compound 45) is a potent and selective inhibitor of BET BD2 (IC₅₀=1.6 nM). BET BD2-IN-1 inhibits the differentiation of Th17 cells by decreasing the activation of STAT3 and NF-κB. BET BD2-IN-1 is used in psoriasis and inflammatory bowel disease (IBD) research.

SJ46420 is a BRD3 PROTAC degrader with a DC₅₀ of 224 nM in U2OS cells. SJ46420 selectively mediates BRD3 degradation, exerts only partial effects on BRD2 and BRD4, and its activity is dependent on KLHDC2. SJ46420 is a prodrug variant of SJ46421 (HY-168634). SJ46420 can be used in the research of prostate cancer.

GW 841819X is a benzodiazepine inhibitor of bromodomains of the BET family (BRD2, BRD3, BRD4) that inhibits the binding of Diazepam to central GABA receptors. GW 841819X can be used in the research of BET bromodomain-related diseases, such as cancer.

WNY0824 (PLK1/BRD4-IN-1) is an orally active dual inhibitor of PLK1 and BET protein families, with IC₅₀ values ​​of 22, 402.5, 150.7, 103.9, and 311.9 nmol/L for PLK1, BRD2, BRD3, BRD4, and BRDT, respectively. WNY0824 induces cell cycle arrest and apoptosis by inhibiting AR- and MYC-mediated transcriptional processes. In addition, WNY0824 also inhibits tumor growth in Enzalutamide (HY-70002) resistant CRPC xenograft tumor models.

PARP1/BRD4-IN-3 (compound HF4) is a potent BRD4 and PARP1 inhibitor with IC₅₀ values of 1210, 2019 nM for BRD4, PARP1, respectively. PARP1/BRD4-IN-3 shows antiproliferative activities. PARP1/BRD4-IN-3 induces apoptosis and cell cycle arrest at G0/G1 phase. PARP1/BRD4-IN-3 causes DNA damage and reduces the protein expression of Rad51. PARP1/BRD4-IN-3 shows antitumor efficacy.

CZL-077 is a potent, selective, and orally active p300/CBP bromodomain (BRD) inhibitor (p300 IC₅₀ = 0.034 μM, CBP IC₅₀ = 0.052 μM) exhibiting high selectivity over the BRDs of BET proteins (BRD2/3/4). CZL-077 inhibits cell growth with IC₅₀ values of 0.024 μM and 5.6 μM in OPM-2 and 22RV1 cells, respectively. CZL-077 shows antitumor efficacy in OPM-2 and 22RV1 xenograft mouse models. CZL-077 can be used for multiple myeloma and prostate cancer research.

GSK778 (iBET-BD1) hydrochloride is a potent and selective BD1 bromodomain inhibitor of the BET proteins, with IC₅₀s of 75 nM (BRD2 BD1), 41 nM (BRD3 BD1), 41 nM (BRD4 BD1), and 143 nM (BRDT BD1), respectively.