| 生化机理 |
Description:
IC50 Value:39 nM (PI3Kα); 383 nM (PI3Kβ); 36 nM (PI3Kδ); 23 nM(PI3Kγ) [1]
XL147 is a potent, orally bioavailable inhibitor of the class I PI3K family of lipid kinases with IC50 values in the nanomolar range in biochemical assays.
in vitro: XL147 binds in an ATP-competitive and reversible manner, yet is highly selective against a panel of >130 human protein kinases. In cellular assays, XL147 antagonizes the production of the second messenger phosphatidylinositol-3,4,5-trisphosphate (PIP3) resulting in inhibition of phosphorylation of several downstream effectors of PI3K including Akt, ribosomal S6 kinase, and ribosomal S6 protein [1].Compared with XL147 alone, the combination exhibited a superior antitumor effect against trastuzumab-resistant tumor xenografts. Furthermore, treatment with XL147 and trastuzumab reduced the cancer stem-cell (CSC) fraction within trastuzumab-resistant cells both in vitro and in vivo [2]. |
