AZD8186

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Chemical Structure| 1627494-13-6 同义名 : -
CAS号 : 1627494-13-6
货号 : A160272
分子式 : C24H25F2N3O4
纯度 : 99%
分子量 : 457.47
MDL号 : MFCD27987908
存储条件：

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

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 35 mg/mL(76.51 mM)，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

  • p110β

    PI3Kβ, IC50:4 nM

  • p110α

    PI3Kα, IC50:35 nM

  • p110δ

    PI3Kδ, IC50:12 nM
描述 Several studies have highlighted the dependency of PTEN deficiency to PI3Kβ activity. For example, conditional knockout of PIK3CB, the gene coding for the p110β subunit, can block the formation of prostate tumours in mouse models, which shows the important role of PI3Kβ in the occurrence of prostate tumour driven by PTEN loss/mutant[1]. AZD8186 is a potent and selective inhibitor of PI3Kβ/δ with IC50 of 4 nM and 12 nM (measured by using a Kinase-Glo Plus Assay Kit), respectively, less potent to PI3Kα (IC50=35 nM)[2]. Treatment of 3 nM of AZD8186 can inhibit 50% level of PI3Kβ-dependent activation of pAKT-Ser473 in PTEN-null, MDA-MB-468, cell line, as well as 17 nM of AZD8186 can inhibit IgM-stimulated pAKT-Ser473, which is activated through PI3Kδ, in JEKO cells. These indicate AZD8186 selectively inhibits PI3Kβ- andδ-mediated signaling through AKT in vitro. In the study of growth inhibition by AZD8186, it was found that AZD8186 is effective in breast and prostate lines, but show more reliable on loss of PTEN in prostate lines. AZD8186 is effective to combination therapy in prostate cancer preclinical models. 10 and 30 mg/kg AZD8186 with 15 mg/kg docetaxel showed regressions in PC3 tumor model[3].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.19mL

0.44mL

0.22mL

10.93mL

2.19mL

1.09mL

21.86mL

4.37mL

2.19mL
参考文献

[1]Wee S, Wiederschain D, et al. PTEN-deficient cancers depend on PIK3CB. Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):13057-62.

[2]Barlaam B, Cosulich S, et al. Discovery of (R)-8-(1-(3,5-difluorophenylamino)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (AZD8186): a potent and selective inhibitor of PI3Kβ and PI3Kδ for the treatment of PTEN-deficient cancers. J Med Chem. 2015 Jan 22;58(2):943-62.

[3]Hancox U, Cosulich S, et al. Inhibition of PI3Kβ signaling with AZD8186 inhibits growth of PTEN-deficient breast and prostate tumors alone and in combination with docetaxel. Mol Cancer Ther. 2015 Jan;14(1):48-58.