protac bet degrader-1

PROTAC BET Degrader-1 is a potent degrader of BET based on PROTAC.

PROTAC BET Degrader-10 (WO2017007612A1, example 37) is a highly efficient and selective small molecule compound designed to degrade BET protein BRD4. PROTAC BET Degrader-10 functions by utilizing specific ligands that connect Cereblon and BRD4, with a DC 50 value of 49 nM.

ARV-771 是基于 PROTAC 技术的有效 BET 降解剂，对 BRD2(1)、BRD2(2)、BRD3(1)、BRD3(2)、BRD4 (1) 和 BRD4(2)的 Kd 分别为 34、4.7、8.3、7.6、9.6 和 7.6 nM。

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 。

(S,R,S)-AHPC-Me dihydrochloride, also known as VHL ligand 2 dihydrochloride, is a chemical compound utilized in the synthesis of ARV-771. ARV-771, a BET PROTAC degrader relying on von Hippel-Landau (VHL) E3 ligase, demonstrates potent degradation of BET protein in castration-resistant prostate cancer (CRPC) cells, with a DC50 of less than 1 nM. This compound serves as the VHL ligand, specifically the (S,R,S)-AHPC-based VHL ligand, that facilitates the recruitment of von Hippel-Lindau (VHL) protein.

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].

PROTAC BRD4 degrader for PAC-1 (compound 5) is a chimeric BET degrader GNE-987 conjugated with a disulfide-containing linker[1]. This PROTAC-linker conjugate specifically targets and degrades BRD4, enabling selective proteolysis of PAC-1.

Thalidomide-NH-C4-NH2 TFA (compound 29c) is a conjugate consisting of an E3 ligase ligand-linker, incorporating the Thalidomide-based cereblon ligand and a linker moiety. This compound, Thalidomide-NH-C4-NH2 TFA, is utilized as a component in PROTAC BRD2 BRD4 degrader-1, which is a highly potent and selective degrader targeting BET proteins BRD4 and BRD2[1].

Thalidomide-O-C6-NH2 TFA is a synthesized E3 ligase ligand-linker conjugate used in the PROTAC dTAG-13, a degrader of FKBP12F36V and BET[1].

Thalidomide-O-C6-NH2 is a synthesized E3 ligase ligand-linker conjugate used in the PROTAC dTAG-13, a degrader of FKBP12F36V and BET[1].

SJ44236 是一种BET的PROTAC降解剂，能够降解BRD2(DC50= 0.127 nM)、BRD3和BRD4。在细胞 MV4-11 和 HD-MB03 中，SJ44236 的细胞毒性IC50分别是 0.12 nM 和 0.92 nM。该化合物下调c-Myc的表达，同时上调p53。SJ44236 在小鼠体内具有良好的口服生物利用度（45%）。(Pink: ligand for target protein JQ-1 carboxylic acid; Black: linker; Blue: ligand for E3 ligaseCereblonE3ligaseLigand 54)

OARV-771 是一种基于 VHL 的 BET 降解剂 (PROTAC)，具有改善的细胞通透性。OARV-771 显示 Brd4、Brd2 和 Brd3的 DC50分别为 6、1 和 4 nM。

(S,R,S)-AHPC-Me是基于 (S,R,S)-AHPC 的的 VHL 配体，可用于募集 von Hippel-Lindau (VHL) 蛋白。它可有效降解去势抵抗性前列腺癌细胞中的 BET 蛋白，DC50<1 nM。它可用于合成 ARV-771。