BRD4 Inhibitor

TAT-PiET is a cell-penetrating peptide targeting the extra-terminal (ET) domain of BRD4. TAT-PiET can reduce BRD4 and JMJD6 levels and inhibit cell proliferation. TAT-PiET also resists the endocrine resistance of ERα-positive breast cancer cells. TAT-PiET can be used for the research of cancer, such as breast cancer.

BRD4 Inhibitor-15 (compound 13) is a potent BRD4 inhibitor, with an IC₅₀ of 18 nM. BRD4 Inhibitor-15 induces apoptosis of 22RV1 cells by regulating Bcl-2/Bax proteins and activating caspase-3 signaling pathway. BRD4 Inhibitor-15 down-regulates the c-Myc level in 22RV1 cells. BRD4 Inhibitor-15 can be used for prostate cancer research.

BRD4-IN-41 is a BRD4 inhibitor with an IC₅₀ of 34 nM. BRD4-IN-41 also inhibits JAK2, FLT3, RET, ROS1, NTRK3, PDGFRb, and FGFR1 kinases with IC₅₀ values ranging from 0.9 nM to 43 nM. BRD4-IN-41 inhibits acetyl-lysine binding site of BRD4, downregulates c-MYC, reduces phosphorylated STAT3 levels, induces G1 cell cycle arrest and apoptosis, thereby inhibiting cancer cells growth. BRD4-IN-41 can be used for the research of cancer, such as multiple myeloma and acute myeloid leukemia.

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.

BRD4 degrader-2 (Compound JP-2-197) is a covalent monovalent molecular glue BRD4degrader that induces a ternary complex formation between BRD4 and RNF126. BRD4 degrader-2 targets RNF126 (E3 ligase) and degrades both the long and short isoforms of BRD4 in cells.

BRD4 Inhibitor-40 (Compound 23) is the inhibitor for BRD that inhibits BRD4-BD1, BRD4-BD2, BRD2-BD1 and BRD2-BD2 with IC₅₀s of 16.1, 142.18, 29.35 and 302.35 nM, respectively. BRD4 Inhibitor-40 modulates the expression of c-Myc and p21, arrests cell cycle at G1 phase, inhibits Pkd1-null (PN) renal cystic epithelial cells, and blocks the renal cysts formation in Madin-Darby canine kidney and embryonic kidney vesicle models. BRD4 Inhibitor-40 exhibits renal cysts inhibitory activity in mouse models.

HL435 is a BRD4 PROTAC degrader with DC₅₀ values of 11.9 nM (MDA-MB-231 cells) and 21.9 nM (MCF-7 cells), respectively. HL435 recruits the CRL4_DCAF11 E3 ubiquitin ligase complex to degrade BRD4 via the ubiquitin-proteasome system. HL435 induces cell cycle arrest and apoptosis (apoptosis) in cancer cells, downregulates the expression levels of cyclin D1 and cyclin B1, activates caspase-9, and induces PARP1 cleavage. HL435 exerts anti-tumor activity both in vitro and in mouse xenograft tumor models. HL435 can be used for the research of breast cancer and prostate cancer.

PI3Kα-IN-28 (Compound 23) is an efficient dual targeted PI3K/BRD4 inhibitor. PI3Kα-IN-28 can inhibit the proliferation of various cells, such as KYSE180 and KYSE450 cells. PI3Kα-IN-28 can concentration dependently inhibit migration and colony formation, induce G0/G1 phase arrest, significantly inhibit DNA synthesis, and significantly increase the proportion of senescent cells. PI3Kα-IN-28 can inhibit the expression of p-AKT and c-Myc and activate the AMPK-p27 pathway. PI3Kα-IN-28 can be used for research on cancers such as esophageal cancer.

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.

HL403 is a potent and dual BRD4/Src inhibitor. HL403 has IC₅₀ values of 133 nM for BRD4 inhibition and 4.5 nM for Src inhibition. HL403 shows anti-cancer activity.

BRD4-IN-11 is an orally active and selective BRD4 inhibitor (IC₅₀ = 26.35 nM (BD1), IC₅₀ = 72.81 nM (BD2)). BRD4-IN-11 is approximately 3- to 18-fold more potent against BRD4 than againstBRD2, BRD3, and BRDT. BRD4-IN-11 enhances H2S release and inhibits the upregulation of fibrotic markers (α-SMA and fibronectin), c-Myc, and CDC25B. BRD4-IN-11 reduces apoptosis in LO2 hepatocytes. BRD4-IN-11 significantly improves liver and lung function in a hepatopulmonary fibrosis model and can be used to study hepatopulmonary fibrosis.

BRD4-IN-10 (Compound 31) is a selective BRD4 inhibitor with an IC₅₀ of 13.5 nM. BRD4-IN-10 can exert anti-inflammatory and anti-fibrotic effects. BRD4-IN-10 also has good metabolic stability, pharmacokinetic properties and safety. BRD4-IN-10 can be used in the research of renal fibrosis diseases.

KWZL-7f15 is a dual CDK6/BRD4 inhibitor with an IC₅₀ of 31.81 nM against human CDK6. KWZL-7f15 inhibits the CDK6-RB axis and BRD4-Myc axis, and also acts as a pan-BET inhibitor. KWZL-7f15 exhibits antiproliferative activity against triple-negative breast cancer cells. KWZL-7f15 shows antitumor activity in xenograft mouse models. KWZL-7f15 can be used in studies related to triple-negative breast cancer.

PARP1/BRD4-IN-2 is a potent and selective PARP1 and BRD4 inhibitor with IC₅₀ values of 197 nM and 238 nM, respectively. PARP1/BRD4-IN-2 inhibits DNA damage repair, arrests G0/G1 transition and induces apoptosis. PARP1/BRD4-IN-2 has anti-tumor activity in MDA-MB-468 xenograft mouse model. PARP1/BRD4-IN-2 can be used for researching triple-negative breast cancer (TNBC).

BET-IN-6 is a BET inhibitor. BET-IN-6 can be used as a Ligand for Target Protein for PROTAC for the synthesis of BRD2/BRD4 PROTAC degraders, such as PROTAC BRD2/BRD4 degrader-1 (HY-130612). BET-IN-6 can be used for cancer research.

PROTAC BRD4 Degrader-37 is a BRD4 PROTAC degrader with a DC₅₀ of 36.4 nM. PROTAC BRD4 Degrader-37 recruits the E3 ubiquitin ligase TRIM21, binds to the PRYSPRY domain of TRIM21 (K_D = 123 nM), and thereby mediates the ubiquitination and degradation of BRD4. PROTAC BRD4 Degrader-37 exhibits cytotoxicity against PANC-1 cells (GI₅₀ = 0.282 μM). PROTAC BRD4 Degrader-37 can be used in studies related to pancreatic cancer.

PROTAC BRD4 Degrader-32 is a CRBN-recruiting PROTAC degrader targeting BRD4 (DC₅₀=0.2 nM in HEK293 cells). PROTAC BRD4 Degrader-32 exhibits an IC₅₀ of 0.05 μM against human CRBN and an IC₅₀ of 22 nM against human BRD4. PROTAC BRD4 Degrader-32 induces reduced degradation of CK1α and WIZ, causes low-level degradation of IKZF1, and does not regulate GSPT1. PROTAC BRD4 Degrader-32 holds promise for research on BRD4-related cancers (such as hematological malignancies).

SB-284851-BT is an inhibitor of BRD4/p38α/BRDT. SB-284851-BT inhibits BRD4-BD1 (IC₅₀=1.7 µM), p38α (K_d=0.47 nM), BRDT (1) (IC₅₀=18 µM) and BRD4 (1)(IC₅₀=3.7 µM). SB-284851-BT reduces IL-8 production by inhibiting p38α, as well as inhibiting BRD4 to down-regulates c-Myc and NF-κB gene pathways in cancer. SB-284851-BT can combined with the bromine domain and extra terminal (BET).

3-Methylcarbostyril (compound 5) is a BRD4 BD1 inhibitor with a pIC₅₀ of 4.4.

BET-IN-15 (compound 1) is a potent and orally active BET inhibitor with IC₅₀ values of 0.64，0.25 nM for BRD4-BD1，BRD4-BD2，respectively. BET-IN-15 shows antiproliferative activity.