BRD4 Inhibitor

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.

GSK1324726A is a novel, potent, and selective inhibitor of BET proteins with high affinity to BRD2 (IC₅₀=41 nM), BRD3 (IC₅₀=31 nM), and BRD4 (IC₅₀=22 nM).

SF2523 is a highly selective and potent inhibitor of PI3K with IC₅₀s of 34 nM, 158 nM, 9 nM, 241 nM and 280 nM for PI3Kα, PI3Kγ, DNA-PK, BRD4 and mTOR, respectively.

GSK973, a chemical probe, is a highly selective, orally bioavailable inhibitor of the BD2s (second bromodomains) of the BET family, with a pIC₅₀ of 7.8 and a pK_d of 8.7 for BRD4 BD2. GSK973 displays a 1600-fold selectivity for BRD4 BD2 over BRD4 BD1. GSK973 shows good potency against BRD2 BD2, BRD3 BD2, and BRDT BD2 (pIC₅₀=7.4~7.8; pK_d=8.3~8.5).

BETd-260 (ZBC 260) is a BET PROTAC degrader. BETd-260 recruits BRD2, BRD3, and BRD4 to the CUL4-RBX1-DDB1-CRBN E3 ubiquitin ligase complex, driving cereblon-, proteasome-, and NEDD8-activating enzyme-dependent ubiquitination and degradation, with a DC50 of approximately 30-100 pM in RS4;11 cells. BETd-260 induces cancer cell apoptosis via endogenous signaling pathways, regulates the expression of the Bcl-2 family, inhibits the oncogene c-Myc, and reduces cell viability. BETd-260 suppresses tumor growth in mouse xenograft models with good biosafety. BETd-260 can be used in research related to acute leukemia, hepatocellular carcinoma, osteosarcoma, and triple-negative breast cancer.

LT052 is a highly selective BET BD1 inhibitor with an IC₅₀ of 87.7 nM. LT052 exhibits nanomolar BRD4 BD1 potency and 138-fold selectivity over BRD4 BD2 (IC₅₀=12.130 μM). LT052 has anti-inflammatory?activity and can be used for acute gout arthritis research.

KPT-276 is an orally active and blood-brain barrier-penetrant selective XPO1/CRM1 inhibitor. KPT-276 blocks XPO1-mediated nuclear export function and promotes nuclear retention of various tumor suppressor proteins. KPT-276 induces apoptosis and G1 cell cycle arrest in tumor cells, and downregulates c-MYC, CDC25A, and BRD4. KPT-276 reduces immune cell proliferation through nuclear accumulation of cell cycle inhibitors, rescues TDP-43 cytoplasmic mislocalization, and restores axon growth and growth rate in mutant PFN1 motor neurons. KPT-276 maintains axonal cytoskeletal integrity and mitochondrial function, and inhibits tumor growth. KPT-276 can be used for research on glioblastoma, non-Hodgkin lymphoma, amyotrophic lateral sclerosis, multiple myeloma, and non-small cell lung cancer.

(S)-JQ-35 (TEN-010) is an orally active, blood-brain barrier-permeable bromodomain inhibitor that selectively targets the bromodomain and extra-terminal domain (BET) protein family (BRD4, BRD3, BRD2 and BRDT). (S)-JQ-35 blocks the activation of Myc gene expression by BRD4, thereby inhibiting cancer cell proliferation and promoting cancer cell apoptosis. (S)-JQ-35 can be used in research related to NUT midline carcinoma and neuroblastoma.

PLK1/BRD4-IN-5 (Compound SC10) is an orally active PLK1 and BRD4 inhibitor with IC₅₀ values of 0.3  nM and 60.8  nM, respectively. PLK1/BRD4-IN-5 can induce MV4-11 cell block in S phase and apoptosis) in a dose-dependent manner. PLK1/BRD4-IN-5 can be used in cancer research.

PROTAC BET Degrader-1 is a BRD2/BRD3/BRD4 PROTAC degrader. PROTAC BET Degrader-1 inhibits the growth of acute leukemia cells. PROTAC BET Degrader-1 is applicable to the research of acute leukemia.

HJB97 is a high-affinity BET inhibitor with K_i values of 0.9 nM (BRD2 BD1), 0.27 nM (BRD2 BD2), 0.18 nM (BRD3 BD1), 0.21 nM (BRD3 BD2), 0.5 nM (BRD4 BD1), and 1.0 nM (BRD4 BD2). HJB97 can serve as a ligand for target protein (Ligands for Target Protein for PROTAC) for the development of PROTAC BET degraders with antitumor activity. HJB97 can be used for the synthesis of BETd-260 (HY-101519).

iBRD4-BD1 is selective BRD4 bromodomain inhibitor. iBRD4-BD1 has inhibition activity for BRD4 bromodomain with an IC₅₀ value of 12 nM. iBRD4-BD1 can be used for the research of inflammation and oncology.

RVX-297 is a potent, orally active BET bromodomain inhibitor with selectivity for BD2. RVX-297 shows IC₅₀s of 0.08, 0.05, and 0.02 μM for BRD2(BD2), BRD3(BD2), and BRD4(BD2), respectively. RVX-297 suppresses inflammatory gene expression in multiple immune cell types. RVX-297 is effective in acute inflammation and autoimmunity models.

BET-IN-31 is a potent BET inhibitor and a ligand for target BRD4 protein for PROTACT GNE-987 (HY-129937A).

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.

JQ1-TCO is the double bond E configuration of JQ1-TCO (HY-148864A). JQ1-TCO is a derivative of JQ1 (HY-13030), an inhibitor of BET. JQ1-TCO is suitable for click chemistry and can be used as molecular probes in vitro and in vivo.

SRX3177 is a triple inhibitor of CDK4/6, PI3K, and BRD4, with IC₅₀s of <2.5 nM (CDK4), 3.3 nM (CDK6), 33 nM (BRD4 BD1), 89 nM (BRD4 BD2), 79 nM (PI3Kα), 83 nM (PI3Kδ), 3.18 μM (PI3Kγ) , respectively. SRX3177 blocks the interaction between the SARS-CoV-2 E protein and the BRD2/4 BD1 domain, restores E protein-attenuated NF-κB activity. SRX3177 exerts broad cytotoxic activity against cancer cells. SRX3177 can be used for the study of anti-SARS-CoV-2 and cancer.

GS-626510 is a potent, and orally active BET family bromodomains inhibitor, with K_d values of 0.59-3.2 nM for BRD2/3/4, with IC₅₀ values of 83 nM and 78 nM foe BD1 and BD2, respectively.

ZEN-2759 is a non-covalent BRD4 inhibitor with IC₅₀ values of 0.23, 0.08, and 0.28 μM for BRD4 (BD1), BRD4 (BD2), and BRD4 (BD1BD2), respectively. ZEN-2759 can be used for cancer research.

PROTAC BRD4 Degrader-1 is a PROTAC connected by ligands for Cereblon and BRD4 with an IC₅₀ of 41.8 nM against BRD4 BD1. PROTAC BRD4 Degrader-1 can effectively degrade BRD4 protein and suppress c-Myc expression.