Molecular Weight (MW)

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

Synonym & Chemical Name

XL147; XL 147; XL-147; SAR245408; SAR-245408; SAR 245408; N-(3-{[(3-{[2-chloro-5-(methoxy)phenyl]amino}quinoxalin-2-yl)amino]sulfonyl}phenyl)-2-methylalaninamide

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.

SAR245408 (XL147) in vitro activity

SAR245408 (XL147) activity in vivo against individual tumor xenografts. Pediatr Blood Cancer. 2013, 60(5), 791-798.