protac er degrader-2

PROTAC ER Degrader-2 serves as a synthesis intermediate for the production of PAC, a compound that incorporates the ADCs linker and PROTACs, which are subsequently conjugated to an antibody. PAC, exhibits a greater capability to degrade estrogen receptor-alpha (ERα) compared to PROTAC (without the presence of an antibody)[1].

PROTAC ERα Degrader-2 comprises a cIAP1 ligand binding group, a linker and an estrogen receptor α (ERα) binding group. PROTAC ERα Degrader-2 is an ERα degrader. Maximal ERα degradation at 30 μM concentration in human mammary tumor MCF7 cells. Degradation inducers based on cIAP1 are called specific and non-genetic IAP-dependent protein erasers (SNIPERs)[1].

ER ligand-2 作为ER的特定配体，可用于合成PROTAC ER Degrader-11。

PROTAC ER Degrader-14 (compound 86) 是一种 PROTAC 类型的 Estrogen Receptor/ERR 降解剂，由以下部分组成：E3 泛素连接酶配体 (blue part)(S)-Deoxy-thalidomide、PROTAC Linker (black part) N-Boc-piperazine，以及靶蛋白配体 (red part) ER ligand-6。E3 连接酶加上 Linker 共同构成了 tert-Butyl (S)-4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperazine-1-carboxylate。

(Rac)-Vepdegestrant 是 Vepdegestrant 的异构体。Vepdegestrant ((Rac)-ARV-471) 是一种口服活性的雌激素受体PROTAC蛋白降解剂，专用于治疗乳腺癌。作为一种异双功能分子，Vepdegestrant 能促进雌激素受体 α 与细胞内 E3 连接酶复合物之间的相互作用，通过蛋白酶体途径促进雌激素受体的泛素化和降解。该化合物可以强效降解 ER 阳性乳腺癌细胞系中的 ER，DC50 值约为 2 nM。