Identification of a Novel Oxadiazole Inhibitor of Mammalian Target of Rapamycin

摘要

We performed a biochemical screen against mTOR using in-house small molecule library.Two novel,structurally distinct hits were identified.Among them,a novel oxadiazole scaffold compound(2) suppressed the phosphorylation of both S6K1 and Aktl in HeLa cells.Docking study suggested that 2 is ATP-competitive and shows a pi-pi interaction with Trp2239 and hydrogen bonds with Trp2239 and Thr2245.Through derivatization,a slightly more potent analogue(2a) was identified with IC_(50) of 9.6 μM.Our study provides a starting point for discovery of novel potent mTOR inhibitors.