A Novel Dual-Targeting PROTAC Overcomes Endocrine Resistance by Engaging Orthosteric and Allosteric Sites of Estrogen Receptor α.
Estrogen receptor α (ERα) remains a pivotal therapeutic target for ER-positive (ER+) breast cancer, yet resistance to endocrine therapies driven by ligand-binding pocket (LBP) mutations demands novel strategies. To integrate the complementary strengths of binding modalities of the orthosteric LBP and the allosteric coa...