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 is composed of a cIAP1 ligand binding group, a linker, and an estrogen receptor α (ERα) binding group, serving as an ERα degrader. It achieves maximal ERα degradation in human mammary tumor MCF7 cells at a concentration of 30 μM. Degradation inducers that utilize cIAP1 are referred to as specific and non-genetic IAP-dependent protein erasers (SNIPERs)[1].

ER ligand-2 is a ligand for ER. It can be used in the synthesis of PROTAC ER Degrader-11.

PROTAC ER Degrader-14 (compound 86) is a PROTAC-type estrogen receptor/ERR degrader. It comprises an E3 ubiquitin ligase ligand (blue part) (S)-Deoxy-thalidomide, a PROTAC linker (black part) N-Boc-piperazine, and a target protein ligand (red part) ER ligand-6. The combination of the E3 ligase and linker forms tert-Butyl (S)-4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperazine-1-carboxylate.

(Rac)-Vepdegestrant is an isomer of Vepdegestrant. Vepdegestrant ((Rac)-ARV-471) is an orally active estrogen receptor PROTAC degrader used against breast cancer. It is a heterobifunctional molecule that facilitates the interaction between estrogen receptor α and the intracellular E3 ligase complex. Vepdegestrant induces ubiquitination and subsequent degradation of the estrogen receptor via the proteasome, effectively degrading ER in ER-positive breast cancer cell lines with a DC50 value of approximately 2 nM.