product name PF-4989216
Description: PF-4989216 is a novel potent and selective PI3K inhibitor with IC50 of 2 nM, 142 nM, 65 nM, 1 nM, and 110 nM for p110α, p110β, p110γ, p110δ, and VPS34, respectively. PF-4989216 inhibits the phosphorylation of PI3K downstream molecules and subsequently leads to inhibition in cell proliferation and xenograft tumor growth in NSCLCs harboring a PIK3CA mutation, including an erlotinib resistant line, NCI-H1975. PF-4989216 inhibited PI3K downstream signaling and subsequently led to apoptosis induction, and inhibition in cell viability, transformation, and xenograft tumor growth in SCLCs harboring PIK3CA mutation.
References: Clin Cancer Res. 2014 Feb 1;20(3):631-43.
380.4
Formula
C18H13FN6OS
CAS No.
1276553-09-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 76 mg/mL (199.8 mM)
Water: <1 mg/mL
Ethanol: 7 mg/mL warming (18.4 mM)
Solubility (In vivo)
Suspended in 0.5% methylcellulose: 1mg/mL
Chemical Name
4-(4-cyano-2-fluorophenyl)-2-morpholino-5-(1H-1,2,4-triazol-3-yl)thiophene-3-carbonitrile
other peoduct :
| In Vitro | Kinase Assay:
Cell Assay: SCLC cells are cultured (5,000 cells/well) in a 96-well microtiter plate at 37°C in 5% CO2 in supplier-recommended growth media and compounds are added to each well starting at 10 μM with a 3-fold serial dilution. At 72 hours after compound addition, CellTiter-Glo (CTG) Solution is added per the manufacturers instructions. Luminescence is read on an Envision plate reader. All experiments are run in duplicate and have been repeated at least three times. Cells NCI-H69, NCI-H1048, NCI-H1436, NCI-H82, NCI-H254, NCI-H526, NCI-H1963, NCI-H146, NCI-H841, Lu99A, Lu134B, and Lu134A cells. PF-4989216 significantly inhibits cell viability in SCLC cells with a PIK3CA mutation, such as NCI-H69, NCI-H1048, and Lu99A cells. PF-4989216, via PI3K signaling inhibition, blocks cell-cycle progression and reduces cell transformation in SCLCs. In SCLCs with PIK3CA mutation, PF-4989216 induces BIM-mediated apoptosis. |
|---|---|
| In Vivo | In SCID mice bearing NCI-H69 or NCI-H1048 xenograft tumors, PF-4989216 (350 mg/kg, p.o.) inhibits PI3K phosphorylation signaling and induces antitumor activity. |
| Animal model | SCID mice bearing NCI-H69 or NCI-H1048 xenograft tumors |
| Formulation & Dosage | Dissolved in in 0.5% methylcellulose; 350 mg/kg; oral administration |
| References | [1] Walls M, et al. Clin Cancer Res. 2014, 20(3), 631-643. |
