WYE-687 dihydrochloride

WYE-687 is an inhibitor of mammalian target of rapamycin (mTOR; IC₅₀ = 0.007 ?M).¹ It is selective for mTOR over PI3Kα and PI3Kγ (IC₅₀s = 0.81 and 3.11 ?M, respectively), as well as a panel of 24 additional kinases (IC₅₀s = >50 ?M for all). WYE-687 (0.2, 1, and 5 ?M) decreases phosphorylation of the mTORC1 and mTORC2 substrates Akt and S6 kinase (S6K1) in a cell-free assay. It decreases proliferation of nine cancer cell lines, including breast, prostate, glioma, kidney, and colorectal cancer cells, with IC₅₀ values ranging from 0.18 to 1.25 ?M. WYE-687 inhibits survival of HL-60 and U937 leukemia cells in a concentration-dependent manner and reduces tumor growth in a U937 mouse xenograft model when administered at doses of 5 and 25 mg/kg.²

1.Yu, K., Toral-Barza, L., Shi, C., et al.Biochemical, cellular, and in vivo activity of novel ATP-competitive and selective inhibitors of the mammalian target of rapamycinCancer Res.69(15)6232-6240(2009) 2.Cheng, F., Wang, L., Shen, Y., et al.Preclinical evaluation of WYE-687, a mTOR kinase inhibitor, as a potential anti-acute myeloid leukemia agentBiochem. Biophys. Res. Commun.470(2)324-330(2016)