PF-4989216 is a 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.

p110α:2 nM, p110γ:65 nM, p110δ:1 nM, p110β:142 nM, VPS34:110 nM

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. [1]

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. [1]

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 manufacturer's instructions. Luminescence is read on an Envision plate reader. All experiments are run in duplicate and have been repeated at least three times.(Only for Reference)