Gedatolisib

mTOR:1.6 nM|PI3Kγ:5.4 nM|PI3Kα:0.4 nM

在MDA-361和PC3-MM2 细胞系中,PKI-587对肿瘤细胞生长有抑制作用（IC50：4/13.1 nM）。PKI-587对PI3Kα突变形式也有效,尤其是H1047R和E545K（IC50：0.6/0.6 nM）。

在H1975(非小细胞肺癌, 突变 EGFR [L858R, T790M])移植瘤模型中,以PKI-587（25 mg/kg）处理7天,实验处理组存活率可达90%.而PKI-587（25 mg/kg,i.v.）会使裸鼠产生高容量分布(7.2 L/kg),低血浆清除力(7(mL/min)/kg)和较长半衰期(14.4 h).在MDA-361移植瘤模型中,PKI-587具有较好的抗肿瘤效果,最低有效剂量为3 mg/kg,最大耐受剂量为30 mg/kg.

DMSO:< 1 mg/mL (insoluble or slightly soluble)

Cells are plated in 96-well culture plates at about 3000 cells per well. One day following plating, PKI-587 is added to cells. Three days after PKI-587 treatment, viable cell densities are determined by measuring metabolic conversion (by viable cells) of the dye MTS, a previously established cell proliferation assay. For each assay, MTS and PMS stocks are freshly thawed and mixed (MTS/PMS, 20:1). The MTS/PMS mixture is then added to 96-well cell plates at 20 μL/well, and plates are incubated for 1 hour–2 hours in cell culture incubator. MTS assay results are read in a 96-well format plate reader by measuring absorbance at 490 nm. The effect of each PKI-587 treatment is calculated as a percentage of control cell growth obtained from vehicle-treated cells grown in the same culture plate.(Only for Reference)