PI3K/mTOR Inhibitor-4

PI3K/mTOR Inhibitor-4 is an orally active pan-class I PI3K/mTOR inhibitor. PI3K/mTOR Inhibitor-4 has enzymatic inhibition activity for PI3Kα , PI3Kγ , PI3Kδ and mTOR with IC 50 values of 0.63 nM, 22 nM, 9.2 nM and 13.85 nM, respectively. PI3K/mTOR Inhibitor-4 can be used for the research of cancer In Vitro PI3K/mTOR Inhibitor-4 (compound 8d-1) has enzymatic inhibition activity for PI3Kα, PI3Kδ, mTOR, PI3Kβ and PI3Kγ with IC 50 values of 0.63 nM, 9.2 nM, 13.85 nM, 94.54 nM and 22 nM, respectively. PI3K/mTOR Inhibitor-4 shows potent anti-proliferation activity in A549, Hela, HCT-116, HepG2, A375 and MCF-7 cells with IC 50 values of 1.35 nM, 1.22 nM, 13.44 nM, 1.08 nM, 18.4 nM and 8.26 nM, respectively. PI3K/mTOR Inhibitor-4 (2.5-10 µM; 24 h) inhibits the PI3K/AKT/mTOR pathway. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: PC12 and LO2 cells Concentration: 0.625-20 µM Incubation Time: 72 h Result: Showed low toxicity in concentrations from 0.625 µM to 20 µM. Western Blot AnalysisCell Line: Hela cells Concentration: 2.5, 5 and 10 µM Incubation Time: 24 h Result: Dose-dependently decreased the level of phosphorylation of AKT and its downstream target S6 in Hela cell line. In Vivo PI3K/mTOR Inhibitor-4 (compound 8d-1) (i.v., oral; 1mg/kg, 10 mg/kg) displays favorable pharmacokinetic parameters in Sprague−Dawley rats . PI3K/mTOR Inhibitor-4 (oral; 10-50 mg/kg) shows significant efficiency in Hela/A549 tumor xenograft models without causing significant weight loss and toxicity . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: SD rats (male; 200-220 g) Dosage: 1, 10 mg/kg Administration: Intravenous, oral Result: IV (1 mg/kg) PO (10 mg/kg) CL (ml/min/kg) Vss (ml/kg) T max (h) C max (ng/ml) AUCinf (ng*h/ml) t 1/2 (h) F(%) 8.6 1199.81 2.67 886.67 4753.35 1.78 24.1 Animal Model: BALB/c nude mice (female; 6-7 weeks; 18-22 g) Dosage: 10, 20, 40, 50 mg/kg/d (Hela model) and 20, 40 mg/kg/d (A549 model) Administration: Oral Result: Inhibited the growth of xenograft tumors in a dose-dependent manner. Form:Solid IC50& Target:PI3Kα 0.63 nM (IC 50 ) PI3Kδ 9.2 nM (IC 50 ) mTOR 13.85 nM (IC 50 ) PI3Kβ 94.54 nM (IC 50 ) PI3Kγ 22 nM (IC 50 )

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