ERα PROTAC

An ERα PROTAC (estrogen receptor alpha proteolysis-targeting chimera) is a class of heterobifunctional small molecules designed to selectively degrade estrogen receptor alpha (ERα), a key driver of hormone receptor-positive (HR+) breast cancer. These molecules consist of an ERα-binding ligand linked to an E3 ubiquitin ligase-recruiting ligand (such as cereblon or von Hippel-Lindau). By bringing ERα into close proximity with the E3 ligase complex, the PROTAC facilitates the polyubiquitination and subsequent proteasomal degradation of ERα. This therapeutic modality offers a more complete elimination of ERα signaling compared to traditional selective estrogen receptor modulators (SERMs) or selective estrogen receptor degraders (SERDs), and has shown preclinical and clinical efficacy against both wild-type and mutated forms of ERα (such as ESR1 mutations) that often drive resistance to standard endocrine therapies.

Other names

ER alpha PROTACER-targeting PROTACERα-targeting PROTACestrogen receptor alpha PROTACestrogen receptor alpha proteolysis-targeting chimera