WYE-125132

WYE-125132 (also known as WYE-132) is a potent, ATP-competitive, and highly selective small molecule dual inhibitor of the mammalian target of rapamycin (mTOR) complexes 1 and 2 (mTORC1/mTORC2). Developed by Wyeth (later acquired by Pfizer), the compound was designed to overcome the limitations of first-generation mTOR inhibitors (rapalogs) by blocking both mTORC1 and mTORC2, thereby preventing the compensatory activation of AKT. Preclinical studies demonstrated significant anti-proliferative and pro-apoptotic activity in various cancer models, including ovarian, breast, and renal cell carcinomas. It also inhibits sphingosine kinase-1 (SphK1) activity, contributing to its cytotoxic effects through the production of pro-apoptotic ceramide. WYE-125132 entered Phase 1 clinical trials for advanced solid tumors, but development was terminated by Pfizer.

Other names

mTOR inhibitor WYE-125132