XL-147, ≥98%
Product Name： XL-147
CAS號:934526-89-3
分子式:C25H25ClN6O4S
分子量:541.02
貯存： 儲存溫度-20°C
可溶性： 25°C： DMSO 3 mg/mL; Water <1 mg/mL; Ethanol <1 mg/mL
生化和生理學(xué)機(jī)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].
in vivo： SAR245408 induced significant differences in EFS distribution compared to control in 29 of 37 (79%) of solid tumor xenografts and in two of seven (29%) ALL. Xenografts. SAR245408 induced tumor growth inhibition meeting criteria for intermediate EFS T/C activity (EFS T/C?>?2) in 4 of 37 (11%) solid tumor xenografts [3].
Toxicity： In vitro SAR245408 demonstrated cytotoxic activity, with a median relative IC50 value of 10.9??M (range 2.7-24.5??M) [4].
Clinical trial： Open-label Treatment Extension Study With SAR-245408 or SAR-245409 as a Monotherapy or as a Combination Regimen. Phase 1/Phase 2
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