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Voxtalisib

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Chemical Structure| 934493-76-2 同义名 : XL765;SAR245409
CAS号 : 934493-76-2
货号 : A393898
分子式 : C13H14N6O
纯度 : 99%+
分子量 : 270.29
MDL号 : MFCD20276656
存储条件：

粉末 Keep in dark place,Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 9 mg/mL(33.3 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • p110γ

    PI3Kγ, IC50:9 nM

  • p110β

    PI3Kβ, IC50:113 nM

  • p110α

    PI3Kα, IC50:39 nM

  • p110δ

    PI3Kδ, IC50:43 nM

  • mTOR

    mTOR, IC50:157 nM
描述 Activation of the PI3K (phosphoinositide 3-kinase) pathway is a frequent occurrence in human tumors and is thought to promote growth, survival, and resistance to diverse therapies. Voxtalisib (XL765) is a potent and highly selective pan inhibitor of class I PI3Ks (α, β, γ, and δ) with activity against mTOR. In cellular assays, XL765 inhibits the formation of PIP3 in the membrane, and inhibits phosphorylation of AKT, p70S6K, and S6 phosphorylation in multiple tumor cell lines with different genetic alterations affecting the PI3K pathway. XL765 displayed potent inhibitory activity against class I PI3K isoforms p110α, p110β, p110δ, and p120γ, with IC50 values of 39, 110, 43, and 9 nM, respectively, IC50 values of 160 and 910 nM for mTORC1 and mTORC2, respectively. In a vitro study, XL765 inhibits colony growth with an IC50 value of 270 nM in PC-3 cells and 230 nM in MCF7 cells. Oral administration of XL765 (10, 30, 100, or 300 mg/kg) caused a dose-dependent decrease of phosphorylation of AKT, p70S6K, and S6 in the tumors on melanoma xenograft mice, reaching a maximum of 84% inhibition of S6 phosphorylation at 30 mg/kg at 4h[3].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.70mL

0.74mL

0.37mL

18.50mL

3.70mL

1.85mL

37.00mL

7.40mL

3.70mL
参考文献

[1]Mirzoeva OK, Hann B, et al. Autophagy suppression promotes apoptotic cell death in response to inhibition of the PI3K-mTOR pathway in pancreatic adenocarcinoma. J Mol Med (Berl). 2011 Sep;89(9):877-89.

[2]Garcia-Echeverria C, Sellers WR. Drug discovery approaches targeting the PI3K/Akt pathway in cancer. Oncogene. 2008 Sep 18;27(41):5511-26.

[3]Yu P, Laird AD, Du X, Wu J, Won KA, Yamaguchi K, Hsu PP, Qian F, Jaeger CT, Zhang W, Buhr CA, Shen P, Abulafia W, Chen J, Young J, Plonowski A, Yakes FM, Chu F, Lee M, Bentzien F, Lam ST, Dale S, Matthews DJ, Lamb P, Foster P. Characterization of the activity of the PI3K/mTOR inhibitor XL765 (SAR245409) in tumor models with diverse genetic alterations affecting the PI3K pathway. Mol Cancer Ther. 2014 May;13(5):1078-91. doi: 10.1158/1535-7163.MCT-13-0709. Epub 2014 Mar 14. PMID: 24634413.