In vitro: 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.
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||76 mg/mL in DMSO|
Overexpression of ATP-binding cassette sub-family G member 2 confers resistance to phosphatidylinositol 3-kinase inhibitor PF-4989216 in cancer cells.
Wu CP, et al. Mol Pharm. 2017 Jun 9. PMID: 28597653.
Targeting small cell lung cancer harboring PIK3CA mutation with a selective oral PI3K inhibitor PF-4989216.
Walls M, et al. Clin Cancer Res. 2014 Feb 1;20(3):631-43. PMID: 24240111.
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