MTOR and neoplasm: As the continued studies, through ring-expansion of the imidazo-ring by insertion of a methylene unit, they [85] discovered a new series of potent and selective mTOR kinase inhibitors (250) with exquisite kinase selectivity (mTOR IC50 ~ 2-176 nM, PI3Kα IC50> = 526 nM), which led to the identification of CC214-2 (251, mTOR IC50=0.002 nM, PI3Kα IC50 =1.38 nM), an orally available mTOR kinase inhibitor with demonstrated anti-tumor activity in mice.