AT-406

AT-406 (formerly known as SM-406) is a novel and orally active antagonist of multiple IAP proteins. AT-406 selectively inhibits the biological activity of IAP proteins, including X chromosome-linked IAP (XIAP), the cellular IAPs 1 (c-IAP1) and 2 (c-IAP2) and melanoma inhibitor of apoptosis protein (ML-IAP). AT-406 effectively antagonizes XIAP BIR3 protein in a cell-free functional assay. AT-406 induced apoptosis is correlated with its ability to down-regulate XIAP whereas AT-406 induces cIAP1 degradation in both AT-406 sensitive and resistance cell lines. AT-406 is highly effective in induction of apoptosis in xenograft tumors, and is capable of complete inhibition of tumor growth. Additionally, AT-406 enhances the carboplatin-induced ovarian cancer cell death and increases survival of the experimental mice in vivo. AT-406 is currently in phase I clinical trials for the treatment of human cancer.