protac brd4 degrader 15

PROTAC BRD4 Degrader-15 is a chemical compound consisting of a PROteolysis TArgeting Chimera (PROTAC) linked to ligands specific to von Hippel-Lindau and BRD4. It exhibits an IC50 of 7.2 nM for BRD4 BD1 and 8.1 nM for BRD4 BD2. Additionally, PROTAC BRD4 Degrader-15 demonstrates potent degradation activity against the BRD4 protein in PC3 prostate cancer cells.

PROTAC BRD2/BRD4 degrader-1 (compound 15) serves as a potent, selective degrader of BET proteins BRD4 and BRD2, achieving rapid, reversible, and unexpectedly selective elimination of BRD4 and BRD2 compared to BRD3. Its efficacy in suppressing solid tumors manifest with minimal cytotoxic effects. This compound comprises a BET inhibitor, a connecting linker, and thalidomide as the ligand for cereblon (CRBN)/cullin 4A[1].

AB3067 是一种用于 BET 蛋白 (BET protein) 的 PROTAC 降解剂，能够募集两种不同的 E3 连接酶 Cereblon 和 VHL，并且表现出良好的亲和力（在活体 HEK293 中，VHL 的 IC50=559 nM，CRBN 的 IC50=190 nM）。此外，AB3067 可以有效降解 BRD2、BRD3、BRD4 和 CRBN，DC50 分别为 2.1~2.3、1.6、15 和 75 nM。该化合物还抑制 RKO 细胞增殖，EC50 为 111 nM。（Pink: ligand for target protein; Black: linker; Blue: ligand for E3ligase VHL and CRBN）

PROTAC BET Degrader-15 是一种 BET PROTAC 降解剂，对 BRD2、BRD3 和 BRD4 的 DC50 分别为 ＜0.10 nM、＜0.01 nM 和 ＜0.01 nM。其能够诱导显著的 G2/M 期细胞周期阻滞及细胞凋亡 (apoptosis)，并显著下调 c-Myc，伴随 p21 上调、CDK6 下调以及凋亡标志物 cleaved PARP 的增加。PROTAC BET Degrader-15 可用于研究血液系统恶性肿瘤和肺癌。