product name Pilaralisib (XL-147)
Description: Pilaralisib (XL147) is a selective and reversible class I PI3K inhibitor for PI3Kα/δ/γ with IC50 of 39 nM/36 nM/23 nM in cell-free assays, less potent to PI3Kβ. Pilaralisib, also known as XL147, is an orally bioavailable small molecule, targeting the class I phosphatidylinositol 3 kinase (PI3K) family of lipid kinases, with potential antineoplastic activity. Class 1 PI3K kinase family inhibitor XL147 reversibly binds to class 1 PI3Ks in an ATP-competitive manner, inhibiting the production of the secondary messenger phosphatidylinositol-3,4,5-trisphosphate (PIP3) and activation of the PI3K signaling pathway.
References: Clin Cancer Res. 2014 Jan 1;20(1):233-45.
541.02
Formula
C25H25ClN6O4S
CAS No.
934526-89-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 100 mg/mL warming (184.8 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
10 mM HCl in sterile water: 0.5mg/mL
Chemical Name
N-(3-{[(3-{[2-chloro-5-(methoxy)phenyl]amino}quinoxalin-2-yl)amino]sulfonyl}phenyl)-2-methylalaninamide
other peoduct :
| In Vitro |
Kinase Assay: 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 Assay: 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 (BT474 cells) are treated with DMSO or pilaralisib. After 5 days of treatment, MTT/WST-1 assays are performed. Pilaralisib exhibits cytotoxic activity in Pediatric Preclinical Testing Program (PPTP) cell lines, with a median relative IC50 value of 10.9 mM (range 2.7 mM to 24.5 mM). |
|---|---|
| In Vivo | In BALB/c nu/nu mice, Pilaralisib (100 mg/kg, p.o.) induces tumor growth inhibition for solid glioma xenografts. Pilaralisib is well tolerated, with only 0.7% toxicity rate in the treated groups, similar to that observed for control animals. In athymic female mouse, Pilaralisib (100 mg/kg, p.o.) significantly delays tumor growth without significant drug-related toxicity. |
| Animal model | BALB/c nu/nu mice with glioma xenografts |
| Formulation & Dosage | Dissolved in 10 mM HCl in sterile water; 100 mg/kg; oral administration |
| References | [1] Reynolds CP, et al. Pediatr Blood Cancer. 2013, 60(5), 791-798.; [2] Foster P, et al. Mol Cancer Ther. 2015, 14(4), 931-940. |
