WYE-354 is an inhibitor of several PI3Ks at micromolar levels. WYE-354 is an effective inhibitor of both mTORC1 and mTORC2 in HEK293 cells. WYE-354 significantly blocks mTOR signaling and Akt activation in U87MG and MDA361 cells. WYE-354 is a potent inhibitor of proliferation in tumor cell lines including MDA-MB-361, MDA-MB-231, MDA-MB-468, LNCap, A498, and HCT116. WYE-354 induces apoptosis which is accompanied by G1 cell cycle arrest and caspases activation. WYE-354 inhibits both mTORC1 and mTORC2 signaling, as revealed by dephosphorylation of S6 ribosomal protein and Akt, respectively, in endothelial HUVEC cells. WYE-354 activates mitogen-activated protein kinase (MAPK) signaling, which may be due to its inhibition of mTORC1.
Soluble in DMSO (99 mg/mL at 25 °C), water (<1 mg/mL at 25 °C), ethanol (~0.4 mg/mL), 1:1 DMF:PBS(pH7.2) (~0.5 mg/mL), and DMF (~30 mg/mL).
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