ERD-9038

Estrogen receptor α (ERα) is a prime target for the treatment of ER-pos. (ER+) breast cancer.Despite the development of several effective therapies targeting ERα signaling, clin. resistance remains a major challenge.In this study, we report the discovery of a new class of potent and orally bioavailable ERα degraders using the PROTAC technol., with ERD-3111 being the most promising compoundERD-3111 exhibits potent in vitro degradation activity against ERα and demonstrates high oral bioavailability in mice, rats, and dogs.Oral administration of ERD-3111 effectively reduces the levels of wild-type and mutated ERα proteins in tumor tissues.ERD-3111 achieves tumor regression or complete tumor growth inhibition in the parental MCF-7 xenograft model with wild-type ER and two clin. relevant ESR1 mutated models in mice.ERD-3111 is a promising ERα degrader for further extensive evaluations for the treatment of ER+ breast cancer.