PI-273 is a first reversibly and specific phosphatidylinositol 4-kinase (PI4KIIα) inhibitor with an IC 50 of 0.47 μM. PI-273 can inhibit breast cancer cell proliferation, block the cell cycle and induce cell apoptosis
In Vitro
PI-273 (2 μM; 48 hours) blocks the cell cycle at the G2-M phase. PI-273 (2 μM; 48 hours) induces cell apoptosis in all three Ras wild-type breast cancer cells: MCF-7, T-47D, and SK-BR-3. PI-273 (0.5-2 μM; for 3 days) can suppress the AKT signaling pathway in a dose- and time-dependent manner. PI-273 of 1 μM and 2 μM inhibits the cell proliferation of both MCF-7 and T-47D cells in a time-dependent manner. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Cycle AnalysisCell Line: MCF-7, T-47D, SK-BR-3, MDA-MB-231, SUM229PE, Hs 578T cells Concentration: 2 μM Incubation Time: 48 hours Result: Blocked the cell cycle at the G2-M phase. Apoptosis AnalysisCell Line: MCF-7, T-47D, and SK-BR-3 cells Concentration: 2 μM Incubation Time: 48 hours Result: Induced cell apoptosis in all three Ras wild-type breast cancer cells: MCF-7, T-47D, and SK-BR-3. Western Blot AnalysisCell Line: MCF-7 cells Concentration: 0.5, 1, 2 μM Incubation Time: For 3 days Result: Suppressed the AKT signaling pathway in a dose- and time-dependent manner.
In Vivo
PI-273 (intraperitoneal injection; 25 mg/kg/day; 15 days) profoundly suppresses the tumor volume and weight in the MCF-7 xenografts . PI-273 (0.5 mg/kg (intravenously) or 1.5 mg/kg (intragastrically); 0.08-5 hours) has a half-life of 0.411 hours for intravenous administration and 1.321 hours for intragastrical administration, and the absolute bioavailability of PI-273 is 5.1% . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Eight-week-old male BALB/c nude mice with MCF-7 cell Dosage: 25 mg/kg Administration: Intraperitoneal injection; daily; 15 days Result: Suppressed the tumor volume and weight in the MCF-7 xenografts. Animal Model: Male Sprague-Dawley (SD) rats Dosage: 0.5 mg/kg (intravenously) or 1.5 mg/kg (intragastrically) (Pharmacokinetic Study) Administration: Intravenously or intragastrically; 0.08, 0.16, 0.33, 0.67, 1, 1.5, 2, 3 and 5 hours Result: Has a half-life of 0.411 hours for intravenous administration and 1.321 hours for intragastrical administration, and the absolute bioavailability of PI-273 is 5.1%.
