GDC-0349 is an ATP-competitive, potent and selective inhibitor of mTOR with an Ki value of 3.8 nM. It has ~800-fold selectivity over PI3Ka and in PC3 cells exhibits an EC50 of 270 nM. Additionally GDC-0349 showed less than 25% inhibition in a panel of 266 kinases, including all isoforms of PI3K. In in vivo PK/PD mouse studies, GDC-0349 inhibits key mTOR biomarkers such as phospho-4EBP1 and phospho-Akt (S473), which supports the notion of concurrent inhibition of both mTORC1 and mTORC2 complexes. (1)