AT416Z

AT416Z is a novel, preclinical-stage selective estrogen receptor modulator (SERM) and a new chemical entity (NCE) structurally related to (Z)-endoxifen. Developed by Atossa Therapeutics in collaboration with the Mayo Clinic, AT416Z is generated as a byproduct during the synthesis of (Z)-endoxifen. In preclinical studies, AT416Z has demonstrated potent anti-estrogenic and anti-cancer activity in estrogen receptor-alpha positive (ERα+) breast cancer models, including those harboring activating ESR1 mutations (such as Y537S and D538G) that are associated with endocrine resistance. The compound inhibits estrogen-induced ERα target gene expression, induces G1 cell cycle arrest, and promotes apoptosis in breast cancer cells, showing potential as a stand-alone therapeutic agent or in combination with other therapies like CDK4/6 inhibitors.