Background:

CH5132799 is an inhibitor of class I phosphatidylinositol 3-kinase (PI3K) with IC50 value of 14nM against PI3Kα [1].

CH5132799 shows inhibitory effect on class I PI3K with IC50 values of 0.014μM, 0.12μM, 0.5μM and 0.036μM against PI3Kα, PI3Kβ, PI3Kδ and PI3Kγ, respectively. PI3Kα is especially sensitive to CH5132799. CH5132799 is a selective inhibitor. It shows less effect on class II PI3Ks, class III PI3K and mTOR. For other 26 protein kinases, CH5132799 nearly has no inhibition with IC50 value of >10μM. CH5132799 is found to have potent antitumor activity. It exerts IC50 values of 0.2μM, 0.032μM, 0.056μM and 0.12μM in HCT116, KPL-4, T-47D and SK-OV-3 cell lines, respectively. Moreover, CH5132799 is oral available in animal models. Treatment of CH5132799 shows strong tumor regression at dose of 12.5 mg/kg in mice bearing human breast cancer xenografts [1].

参考文献:
[1] Ohwada J, Ebiike H, Kawada H, et al. Discovery and biological activity of a novel class I PI3K inhibitor, CH5132799. Bioorganic & medicinal chemistry letters, 2011, 21(6): 1767-1772.