WYE-354

Administered via intraperitoneal injection

Tumor cell lines including MDA-MB-361, MDA-MB-231, MDA-MB-468, LNCap, DU145, A498, and HCT116

WYE-354 is a potent, specific and ATP-competitive inhibitor of mTOR with IC50 of 5 nM.

Dissolved in 5% ethanol, 5% polysorbate 80, 5% PEG-400

WYE-354 also inhibits several PI3Ks at micromolar levels. In HEK293 cells, WYE-354 (0.2 uM–5 uM) effectively inhibits both mTORC1 and mTORC2. WYE-354 (0.3 uM–10 uM) significantly blocks mTOR signaling and Akt activation in U87MG and MDA361 cells. Furthermore, WYE-354 potently inhibits proliferation in tumor cell lines including MDA-MB-361, MDA-MB-231, MDA-MB-468, LNCap, A498, and HCT116, with IC50 values ranging from 0.28 uM to 2.3 uM. The apoptosis induced by WYE-354 is accompanied by G1 cell cycle arrest and caspases activation. [1] In endothelial HUVEC cells, WYE-354 (10 nM–1 uM) also inhibits both mTORC1 and mTORC2 signaling, as revealed by dephosphorylation of S6 ribosomal protein and Akt, respectively. Furthermore, WYE-354 (10 nM–1 uM) activates mitogen-activated protein kinase (MAPK) signaling, which may be due to its inhibition of mTORC1. [2]

72 hours

Cells are plated in 96-well plates at 1000 to 3000 cells per well for 24 hours, treated with DMSO or varying concentrations of WYE-354. Viable cell densities are determined 72 hours later by MTS assay employing a CellTiter 96 kit. The effect of each treatment is calculated as percent of control growth relative to the DMSO-treated cells grown in the same culture plate. Inhibitor dose response curves are plotted for determination of IC50 values.

WYE-354 Chemical Structure

, , Dr. Pierre P. Roger from Free University of Brussels, WYE-354purchased from Selleck, HCT116 were left untreated (C) or stimulated for 5 h with serum (FBS) and rapamycin or WYE-354 at the indicated concentrations.

2 years -20CPowder, 2 weeks4Cin DMSO, 2 months-80Cin DMSO