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Overview
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Background
WYE-687 is an ATP-competitive inhibitor of mTOR with IC50 value of 7nM [1].WYE-687 is a small-molecule pyrazolopyrimidine inhibitor of mTOR1 and mTOR2. In the immune-complex kinase assay using His6-AKT and His6-S6K as the specific substrates of mTOR1 and mTOR2, WYE-687 prevents mTOR from phosphorylating the substrates dose-dependently. Besides that, WYE-687 is found to highly selective against PI3Kα (>100-fold) and PI3Kγ (>500-fold) as well as 24 other protein kinases. It is found that WYE-687 can suppress cell growth via causing a strong G1 arrest in cell cycle in tumor cell lines including MDA361 and HCT116. WYE-687 also affects the angiogenic factor of cancer cells. It reduces the expression of HIF-1α in U87MG, MDA361 and LNCap cells [1].
[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 rapamycin. Cancer research, 2009, 69(15): 6232-6240.
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