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The mammalian target of rapamycin (mTOR) is a serine-threonine kinase that is central to two protein complexes, mTORC1 and mTORC2. These complexes are differentially regulated (e.g., only mTORC1 is sensitive to rapamycin ) and regulate different pathways. WYE-125132 is an ATP-competitive inhibitor of mTOR (IC50 = 0.19 nM) that inhibits signaling through both mTORC1 and mTORC2. It is selective for mTOR over phosphatidylinositol 3-kinase isoforms. WYE-125132 is effective against mTORC1 and mTORC2 in diverse cancer models, both in vitro and in vivo. Oral administration of WYE-125132 alone blocks mTOR signaling and prevents tumor growth in breast, lung, renal, and glioma cancer xenografts in mice, while combination therapy with the VEGF-inhibitor bevacizumab causes complete regression of A498 renal carcinoma tumors. In addition to its applications in cancer, WYE-125132 has been used to delineate novel aspects of mTOR signaling.