brd4-in-4

BRD4-IN-4 是一种具有选择性的 BRD4 抑制剂 ，对 BRD4 的IC50值为 6.83 μM。BRD4-IN-4 选择性抑制 MV4-11 细胞系增殖并将细胞阻滞在 G1 期。BRD4-IN-4可用于研究 MLL 白血病。

ODM-207 (BET-IN-4) 是一种 BET 溴区结构域蛋白的抑制剂，对 BRD4的 IC50值 ≤ 1 μM。

BRD4 Inhibitor-20是一种有效的溴结构域蛋白4(BRD4)抑制剂，具有口服活性。BRD4 Inhibitor-20在癌细胞系中具有抗增殖活性，并被用于各种癌症的研究，如结肠癌。

BET-IN-6 是一种有效且高亲和力的BRD2 BRD4抑制剂。BET-IN-6 是靶蛋白 BRD2 4 的配体，可用于合成 PROTAC BRD2 BRD4 degrader-1 。

GNE-207 is a selective and orally bioavailable inhibitor of the bromodomain of CBP (IC50: 1 nM). It has a selective index of >2500-fold against BRD4 (1). GNE-207 displays excellent CBP potency (EC50: 18 nM for MYC expression in MV-4-11 cells).

BRD4-Kinases-IN-3 is a dual BRD4-Kinases inhibitor that can be used as a value-added multi-targeted chemical probe for cancer therapy.

TW9 is a dual inhibitor of bromodomain 2 (BD2) in bromodomain-containing protein 4 (BRD4) and histone deacetylase 1 (HDAC1; IC50s = 0.074 and 0.29 μM, respectively).1It is selective for BD2 over BD1 in BRD4 (IC50= 0.72 μM) and for HDAC1 over HDAC2 (IC50= 2.5 μM). TW9 (50 nM) induces apoptosis in, and inhibits proliferation of, MIA PaCa-2 pancreatic cancer cells. It induces cell cycle arrest at the G1phase in HPAC pancreatic cancer cells when used at a concentration of 2 μM. TW9 acts synergistically with gemcitabine to reduce the viability of HPAC cells. 1.Zhang, X., Zegar, T., Weiser, T., et al.Characterization of a dual BET HDAC inhibitor for treatment of pancreatic ductal adenocarcinomaInt. J. Cancer147(10)2847-2861(2020)

PROTAC BRD4 Degrader-8 is a potent BRD4 inhibitor, with IC50s of 1.1 nM and 1.4 nM for BRD4 BD1 and BD2, respectively. PROTAC BRD4 Degrader-8 is capable of potently degrading the BRD4 protein in PC3 prostate cancer cells[1]. PROTAC BRD4 Degrader-8 (compound 8; 6 days) inhibits the proliferation of PC3 prostate cancer cells, with an IC50 of 28 nM[1].PROTAC BRD4 Degrader-8 (4 h) suppresses MYC gene transcript in MV4-11 AML cells, with an IC50 of 11 nM[1].PROTAC BRD4 Degrader-8 (4 h) potently degrades the BRD4 protein in PC3 prostate cancer cells, with an DC50 of 7.5 nM[1]. [1]. Dragovich PS, et, al. Antibody-Mediated Delivery of Chimeric BRD4 Degraders. Part 2: Improvement of In Vitro Antiproliferation Activity and In Vivo Antitumor Efficacy. J Med Chem. 2021 Mar 11;64(5):2576-2607.

EN219 is a synthetic recruiter of the E3 ubiquitin ligase RNF114.1It binds to cysteine 8 (C8) in the intrinsically disordered region of RNF114 (RNF114-C8; IC50= 470 nM) and inhibits RNF114-induced autoubiquitination and p21 ubiquitination in a cell-free assay when used at a concentration of 50 μM. EN219 (1 μM) also interacts with cysteine residues in the tubulin β1 chain (TUBB1), heat shock protein 60 (Hsp60), also known as Hsp family D member 1 (HspD1), and histone H3.1 (HIST1H3A) in 231MFP human breast cancer cells in a proteomic profiling assay. It has been linked to the bromodomain and extra terminal domain (BET) inhibitor ligand (+)-JQ1 for use as a proteolysis-targeting chimera (PROTAC) to degrade bromodomain-containing protein 4 (BRD4) in 231MFP cells. 1.Luo, M., Spradlin, J.N., Boike, L., et al.Chemoproteomics-enabled discovery of covalent RNF114-based degraders that mimic natural product functionCell Chem. Biol.28(4)559-566(2021)

CAY17c is an inhibitor of bromodomain-containing protein 4 (BRD4; IC50= 0.71 μM), as well as class I histone deacetylases (HDACs; IC50s = 0.046, 0.058, 0.075, and 0.167 μM for HDAC1, -2, -3, and -8, respectively) and class IIb HDACs (IC50s = 0.073 and 0.923 μM for HDAC6 and HDAC10, respectively).1It is selective for these enzymes over BRD2, -3, and -T (IC50s = >20 μM for all), as well as over HDAC4, -5, -7, -9, and -11 (IC50s = >10 μM for all). CAY17c inhibits the proliferation of HCT116, SW620, and DLD-1 colorectal cancer cells (IC50s = 0.45, 1.78, and 2.11 μM, respectively), as well as induces apoptosis and autophagy in HCT116 cells. It reduces tumor growth in an HCT116 mouse xenograft model when administered at doses of 15 and 30 mg/kg. 1.Pan, Z., Li, X., Wang, Y., et al.Discovery of thieno[2,3-d]pyrimidine-based hydroxamic acid derivatives as bromodomain-containing protein 4/histone deacetylase dual inhibitors induce autophagic cell death in colorectal carcinoma cellsJ. Med. Chem.63(7)3678-3700(2020)

BRD4-IN-2 is a bromodomain BRD4 inhibitor with an IC 50 value of 9.9 nM.

BRD4Inhibitor-26 是一种溴结构域蛋白 4(BRD4)抑制剂 一氧化氮供体。BRD4Inhibitor-26 抑制BRD4(BD1) 和BRD4(BD2)，IC50值分别为 0.82 μM 和 1.94 μM。BRD4Inhibitor-26 可用于卵巢癌的研究。

PROTACBRD4 Degrader-17 (compound 13i)，作为一种高效的 PROTACBRD4 降解剂，其 IC50 值分别为 29.54 nM（针对 BRD4(BD1)）和 3.82 nM（针对 BRD4(BD2)）。该化合物有效抑制 G2 M 相的细胞周期蛋白 B1 (Cyclin B1) 的表达，并在 MV-4-11 细胞中显著诱导细胞凋亡（apoptosis）。

PROTACBRD4Degrader-16是一种高效的PROTAC BRD4降解剂，具有对BRD4(BD1)和BRD4(BD2)分别为34.58 nM及40.23 nM的IC50值。该化合物有效抑制G2 M阶段细胞周期蛋白B1（Cyclin B1）的表达，并显著诱导MV-4-11细胞的细胞凋亡（apoptosis）。

PLK1 BRD4-IN-3 (Compound 21) 既是 BRD4（bromodomain 4）又是 PLK1（polo样激酶1）的选择性双重抑制剂。在对BRD4-BD1、PLK1和BRDT-BD1的抑制作用中，PLK1 BRD4-IN-3的IC50分别为0.059、0.127和0.245 μM。