Pilaralisib (XL-147) is an orally available small molecule that selectively inhibits the activity of phosphoinositide-3 kinase (PI3K). Pilaralisib has been used in trials studying the treatment of Cancer, Lymphoma, Solid Tumors, Glioblastoma, and Breast Cancer, among others.

PI3Kγ:23 nM, PI3Kα:39 nM, PI3Kβ:36 nM, PI3Kδ:36 nM

Pilaralisib 在小儿临床前测试计划 (PPTP) 细胞系展示出细胞毒活性，中位相对IC50值为10.9 mM（范围从2.7 mM到24.5 mM）。[2]

在 BALB/c nu/nu 小鼠中，Pilaralisib（100 mg/kg，p.o.）能有效抑制实体胶质瘤异种移植物的生长。Pilaralisib 的耐受性良好，治疗组的毒性率仅为0.7%。[2] 在无胸腺雌性小鼠中，Pilaralisib（100 mg/kg，p.o.）显著延缓肿瘤生长，且未观察到显著的药物相关毒性。[3]

In vitro kinase inhibition assays: Kinase activity for PI3K isoforms is measured as the percentage of ATP consumed following the kinase reaction using luciferase–luciferin-coupled chemiluminescence, with ATP concentrations approximately equal to the Km for each respective kinase. Kinase reactions are initiated by combining test compounds, ATP and kinase in a 20 μL volume. PI3Kα, PI3Kβ, PI3Kγ, and PI3Kδ final enzyme concentrations are 0.5, 8, 20, and 2 nM, respectively. Of note, 0.5 μL dimethyl sulfoxide (DMSO) containing varying concentrations of the test compound is mixed with 10 μL enzyme solution (2×concentration). Kinase reactions are initiated by the addition of 10 μL of liver phosphatidylinositol and ATP solution (2×concentration). Assay concentrations for VPS34, ATP, and phosphatidylinositol are 40 nM, 1 μM, and 5 μM, respectively

Cell proliferation is measured by using MTT or pre-mixed WST-1 reagent. For MTT/WST-1 assays, 10,000 cells/well are seeded in 96-well plates. 24 h after plating, cells are treated with DMSO or pilaralisib. After 5 days of treatment, MTT/WST-1 assays are performed.(Only for Reference)