WYE-354

PI3Kα:1.89 μM|mTOR:5 nM|PI3Kγ:7.37 μM

WYE-354 (50 mg/kg) 在PTEN-null PC3 mM2肿瘤的小鼠异种移植模型中，强效抑制mTOR信号传导和肿瘤生长。

在HEK293细胞中，WYE-354（0.2 μM–5 μM）有效抑制了mTORC1和mTORC2。在U87 mg和MDA361细胞中，WYE-354（0.3 μM–10 μM）显著阻断了mTOR信号传导和Akt激活。在包括MDA-MB-361、MDA-MB-231、MDA-MB-468、LNCap、A498和HCT116在内的肿瘤细胞系中，WYE-354有效抑制了增殖，IC50值范围为0.28 μM至2.3 μM。在内皮HUVEC细胞中，WYE-354也抑制了mTORC1和mTORC2信号传导，IC50值从10 nM到1 μM不等，这一效果通过S6核糖体蛋白和Akt的去磷酸化得到验证。WYE-354引起的凋亡伴随着G1期细胞周期阻滞和caspases激活。WYE-354（10 nM–1 μM）激活了丝裂原激活蛋白激酶（MAPK）信号传导，这可能是由于其对mTORC1的抑制作用。

DMSO:92 mg/mL (185.66 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);Ethanol:< 1 mg/mL (insoluble or slightly soluble)

Tumor cell lines including MDA-MB-361, MDA-MB-231, MDA-MB-468, LNCap, DU145, A498, and HCT116, 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(0–50 μM, dissolved in DMSO) for72 hours.

Nude mice (BALB/c, nu/nu, female) bearing PC3 mM2 xenograft were intraperitoneally injected with WYE-354（50 mg/kg）dissolved in 5% ethanol, 5% polysorbate 80, 5% PEG-400.