UM-ERD-3111

UM-ERD-3111 (also known as ERD-3111) is a potent, orally bioavailable proteolysis-targeting chimera (PROTAC) designed to degrade estrogen receptor alpha (ERα). Developed by the University of Michigan in collaboration with Proteovant Therapeutics (now SK Life Science Laboratories), UM-ERD-3111 utilizes a high-affinity ER ligand tethered to a cereblon (CRBN) E3 ligase ligand. It exhibits sub-nanomolar degradation potency (DC50 of 0.5 nM) against both wild-type and clinically relevant ESR1-mutated ERα (such as Y537S and D538G). In preclinical models of ER-positive breast cancer, oral administration of UM-ERD-3111 effectively reduced ERα protein levels in tumor tissues and induced robust, sustained tumor regression, demonstrating superior efficacy compared to other clinical-stage ER PROTACs like vepdegestrant (ARV-471).