XL147 (Pilaralisib)

XL147 (Pilaralisib)

【产品别名】SAR245408; XL 147; XL147; SAR-245408; SAR 245408;XL-147

【CAS号】 934526-89-3

【目录编号】

【纯度】 99.02%

【分子式】 C25H25ClN6O4S

【分子量】 541.02

【简介】 XL147(SAR245408; pilaralisib)是口服生物相容性的PI3K抑制剂,对PI3Kα,β,δ和γ的IC50分别为39nM,383nM,36nM和23nM。

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XL147 (Pilaralisib) 详细介绍

生物活性:

XL147(SAR245408; pilaralisib) is a potent, orally bioavailable inhibitor of the class I PI3K family of lipid kinases with IC50 values of 39 nM/383 nM/36 nM/23 nM for PI3Kα/β/δ/γ,  respectively; less potent to PI3Kβ.
IC50 Value:39 nM (PI3Kα); 383 nM (PI3Kβ); 36 nM (PI3Kδ); 23 nM(PI3Kγ) [1]
Target:
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

参考文献:


[1]. Geoffrey I Shapiro, et al. Targeting Aberrant PI3K Pathway Signaling With XL147, a Potent, Selective, and Orally Bioavailable PI3K Inhibitor.

[2]. Chakrabarty A, Trastuzumab-resistant cells rely on a HER2-PI3K-FoxO-survivin axis and are sensitive to PI3K inhibitors. Cancer Res. 2013 Feb 1;73(3):1190-200.

[3]. Reynolds CP, et al. Initial testing (stage 1) of the phosphatidylinositol 3' kinase inhibitor, SAR245408 (XL147) by the pediatric preclinical testing program. Pediatr Blood Cancer. 2013 May;60(5):791-8.

[4]. Reynolds CP, et al. Initial testing (stage 1) of the phosphatidylinositol 3' kinase inhibitor, SAR245408 (XL147) by the pediatric preclinical testing program. Pediatr Blood Cancer. 2013 May;60(5):791-8.


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