CH5132799 是一种选择性的 I 类PI3K抑制剂。它能够抑制 PI3Kα，其 IC50=14 nM。

CH5132799 has been used in trials studying the treatment of Solid Tumors.

CH5132799作为临床备用药,表现出良好的口服生物利用度(小鼠中101%) 人肝微粒体稳定性和体内抗肿瘤活性.CH5132799在小鼠,大鼠,猴子和狗体内,表现出良好的口服生物利用度(F: 54.2-101%).在人乳腺癌(KPL-4: PI3Ka H1047R)异种移植小鼠模型中,用CH5132799（12.5 mg/kg,q.d.）口服治疗显示强烈的肿瘤消退.CH5132799在几种不同的负荷PIK3CA突变型的异种移植模型中,表现出有效的体内抗肿瘤活性.CH5132799在几种具有PIK3CA突变的异种移植模型中显示出强效的体内抗肿瘤活性.

CH5132799处理PIK3CA突变的乳腺癌KPL-4细胞,磷酸化Akt及其直接底物和PRAS40和FoxO1/3a和磷酸化下游因子（包括S6K,S6和4E-BP1）,都被有效抑制。PIK3CA突变型的癌细胞系明显对CH5132799敏感。在通过突变活化PI3K途径的人肿瘤细胞系中,CH5132799显示有效的抗增殖活性。CH5132799有效抑制KPL-4细胞中的AKT磷酸化。CH5132799选择性抑制I类PI3Ks,PI3Kα：IC50 = 0.014 μM,PI3Kβ：IC50 = 0.12 μM,PI3Kδ：IC50 = 0.50 μM,PI3Kγ：IC50 = 0.036 μM,但是对II类PI3Ks,III类PI3k和mTOR的抑制作用较弱,对26种蛋白激酶也没有抑制活性（IC50 >10 μM）。与野生型PI3Kα相比,CH5132799对致癌基因突变体E542K（IC50 = 6.7 nM）,E545K（IC50 = 6.7 nM）和H1047R（IC50 = 5.6 nM）显示出更强的针对PI3Kα的抑制活性。

PI3K Assay: The E542K, E545K, and H1047R mutants of PI3Kα are prepared with an overlapped extension-polymerase chain reaction. Glutathione S-transferase-tagged PI3Kα mutants and His-tagged p85α are co-expressed with BAC-TO-BAC Baculovirus Expression System. The inhibitory activities of CH5132799 on PI3Kα (p110α/p85α), PI3Kβ(p110β/p85α), PI3Kδ (p110δ/p85α), PI3Kγ (p110γ), PI3KC2α, PI3KC2β, Vps34, and PI3Kα mutants are determined by Adapta Universal Kinase Assay Kit. Time-resolved fluorescence is measured with an EnVision HTS microplate reader. IC50 values are calculated using XLfit.

The cell lines are added to the wells of 96-well plates containing 0.076 to 10,000 nM CH5132799 and incubated at 37 °C. After 4 days of incubation, Cell Counting Kit-8 solution is added and, after incubation for several more hours, absorbance at 450 nm is measured with Microplate-Reader iMark. The antiproliferative activity is calculated by the formula (1- T/C) × 100 (%), in which T and C represent absorbance at 450 nm of the cells treated with CH5132799 (T) and that of untreated control cells (C). The IC50 values are calculated by using Microsoft Excel 2007. (Only for Reference)

1007207-67-1

C15H19N7O3S

377.42

Ethanol:<1 mgml
DMSO:10 mg/mL (26.5 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years