WYE-354是ATP竞争性mTOR抑制剂，IC50为5 nM，能阻断mTORC1/P-S6K(T389)和mTORC2/P-AKT(S473)，比对PI3Kα和PI3Kγ的抑制性强100倍和500倍。

99%

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

DMSO:100 mg/mL
Water:<1 mg>Ethanol:<1 mg>

mTOR

WYE-354 also inhibits several PI3Ks at micromolar levels. In HEK293 cells, WYE-354 (0.2 μM–5 μM) effectively inhibits both mTORC1 and mTORC2. WYE-354 (0.3 μM–10 μM) 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 μM to 2.3 μM. The apoptosis induced by WYE-354 is accompanied by G1 cell cycle arrest and caspases activation. In endothelial HUVEC cells, WYE-354 (10 nM–1 μM) also inhibits both mTORC1 and mTORC2 signaling, as revealed by dephosphorylation of S6 ribosomal protein and Akt, respectively. Furthermore, WYE-354 (10 nM–1 μM) activates mitogen-activated protein kinase (MAPK) signaling, which may be due to its inhibition of mTORC1.

In a mice xenograft model of PTEN-null PC3MM2 tumor, WYE-354 (50 mg/kg) effectively inhibits mTOR signaling and tumor growth.

[1] Yu K, et al. Cancer Res, 2009, 69(15), 6232-6240.