AZD4241

AZD4241 is a novel, potent, and orally bioavailable proteolysis-targeting chimera (PROTAC) designed to degrade both wild-type and mutant estrogen receptor alpha (ERα). Developed by AstraZeneca for the treatment of hormone receptor-positive (HR+) breast cancer, it functions by recruiting the cereblon (CRBN) E3 ubiquitin ligase to ERα, leading to its ubiquitination and subsequent degradation by the proteasome. Preclinical studies demonstrate that AZD4241 effectively suppresses ER-dependent gene expression and inhibits tumor growth in various models, including those with ESR1 mutations (e.g., Y537S, D538G) and resistance to CDK4/6 inhibitors like palbociclib. It is positioned as a potential next-generation endocrine therapy to overcome resistance mechanisms associated with current standards of care and is scheduled to enter clinical evaluation in 2026.