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 Akt1 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 IC50 of 9.6 μM. Our study provides a starting point for discovery of novel potent mTOR inhibitors.