Potent, ATP-competitive inhibitor of mammalian target of rapamycin (mTOR) (IC50
= 7 nM). Displays selectivity for mTOR over PI 3-Kα
(~100-fold) and PI 3-Kγ
(~500-fold). Inhibits phosphorylation of mTORC1 and mTORC2 substrates including S6K, SGK and Akt; blocks VEGF secretion and HIF-1α
expression. Exhibits antiproliferative effects in cancer cell lines through G1
cell cycle arrest and selective apoptosis.
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Biochemical, cellular, and in vivo activity of novel ATP-competitive and selective inhibitors of the mammalian target of rapamycin.
Yu et al.
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