AT402Z

AT402Z is a novel, preclinical-stage (Z)-endoxifen-related new chemical entity (NCE) being developed for the treatment of estrogen receptor-alpha positive (ERα+) breast cancer. Generated as a byproduct during the synthesis of (Z)-endoxifen, AT402Z acts as a selective estrogen receptor modulator (SERM) or selective estrogen receptor degrader (SERD). In preclinical studies conducted in collaboration with the Mayo Clinic, AT402Z demonstrated potent anti-estrogenic and anti-proliferative activity in ERα+ breast cancer cell lines, including those harboring ESR1 mutations (such as Y537S and D538G) that are typically associated with endocrine resistance. It has shown efficacy in reducing tumor cell proliferation, promoting cell cycle arrest, and inducing apoptosis, both as a monotherapy and in combination with CDK4/6 inhibitors like abemaciclib.