protac er degrader-3

PROTAC ER Degrader-3, an intermediate for the synthesis of PAC, specifically compound LP2. PAC serves as the linker for ADCs and PROTACs that are conjugated to an antibody. Notably, when PAC is conjugated to an antibody, it exhibits enhanced degradation of estrogen receptor-alpha (ERα) compared to PROTAC alone [1].

ER ligand-3, serving as the ligand for the target protein in PROTAC (Ligand for Target Protein for PROTAC), is utilized for the synthesis of PROTACER Degrader-12.

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.

BY13 is an SRC-3 PROTAC degrader with a DC50 of 0.031 μM. It selectively obstructs the ER signaling pathway by downregulating ERα levels, showing greater selectivity over the androgen receptor (AR). BY13 effectively addresses endocrine resistance in breast cancer by inducing cell cycle arrest at the G1 phase and triggering apoptosis. Additionally, it surpasses Fulvestrant in efficacy and significantly inhibits the growth of resistant breast tumors in LCC2 xenograft mouse models, exhibiting no noticeable toxicity.