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Chemical Structure| 1007207-67-1 同义名 : CH5132799;MEN1611;PA799
CAS号 : 1007207-67-1
货号 : A197431
分子式 : C15H19N7O3S
纯度 : 99%+
分子量 : 377.421
MDL号 : MFCD22419020
存储条件：

粉末 Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 4 mg/mL(10.6 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：

1% DMSO+30% polyethylene glycol+1% Tween 80+water 30 mg/mL suspension

生物活性
靶点

  • p110γ

    PI3Kγ, IC50:36 nM

  • p110β

    PI3Kβ, IC50:0.12 μM

  • p110α

    PI3Kα, IC50:14 nM

  • p110δ

    PI3Kδ, IC50:0.50 μM
描述 The deregulation of phosphatidylinositol 3-kinase (PI3K)/Akt pathway is commonly seen in various human cancers. CH5132799 is a PI3K inhibitor that inhibits PI3Kα, β, δ, γ with IC50 values of 14 nM, 0.12 mM, 0.5 mM and 36 nM, respectively. In breast cancer KPL-4 cells harboring PIK3CA mutation, treatment of 0.001 – 10 mM CH5132799 for 2h suppressed the phosphorylation of Akt and its downstream factors, S6K, S6 and 4E-BP1. When KPL-4 cells were treated with 1 mM CH5132799 for 48h, the G1 arrest and Caspase 3/7 activity were induced. CH5132799 also demonstrated anti-proliferative effect in 60 breast, ovarian, prostate, and endometrial cancer cell lines with 75% of lines having an IC50 value less than 1mM and 38% of lines having an IC50 under 0.3 mM. In the xenograft model of KPL-4 cells harboring the PIK3CA H1047R mutation, daily oral administration of CH5132799 (0.39 – 25 mg/kg/day) showed anti-tumor effect since day 21 post tumor implantation. The inhibition of the PI3K pathway and Akt phosphorylation were also observed in this xenografts model treated by CH5132799. Oral administration of CH5132799 (12.5 mg/kg/day, 12 consecutive days) in mice bearing trastuzumab-insensitive KPL-4 tumors induced remarkable reduction in the tumor volume, and eventually the disappearance of the tumors[3].
作用机制 CH5132799 is a selective, ATP-competitive inhibitor of class I PI3K that interacts with the ATP-binding site of PI3K[3].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.65mL

0.53mL

0.26mL

13.25mL

2.65mL

1.32mL

26.50mL

5.30mL

2.65mL
参考文献

[1]Tanaka H, Yoshida M, et al. The selective class I PI3K inhibitor CH5132799 targets human cancers harboring oncogenic PIK3CA mutations. Clin Cancer Res. 2011 May 15;17(10):3272-81.

[2]Ohwada J, Ebiike H, et al. Discovery and biological activity of a novel class I PI3K inhibitor, CH5132799. Bioorg Med Chem Lett. 2011 Mar 15;21(6):1767-72. doi: 10.1016/j.bmcl.2011.01.065. Epub 2011 Jan 22.

[3]Tanaka H, Yoshida M, Tanimura H, Fujii T, Sakata K, Tachibana Y, Ohwada J, Ebiike H, Kuramoto S, Morita K, Yoshimura Y, Yamazaki T, Ishii N, Kondoh O, Aoki Y. The selective class I PI3K inhibitor CH5132799 targets human cancers harboring oncogenic PIK3CA mutations. Clin Cancer Res. 2011 May 15;17(10):3272-81.