| Identification | Back Directory | [Name]
Benzenesulfonamide, N-[5-[3,4-dihydro-4-(4-methoxyphenyl)-3-oxo-2H-1,4-benzoxazin-6-yl]-2-methoxy-3-pyridinyl]-4-fluoro- | [CAS]
2361215-32-7 | [Synonyms]
PI3K/mTOR Inhibitor-4
Benzenesulfonamide, N-[5-[3,4-dihydro-4-(4-methoxyphenyl)-3-oxo-2H-1,4-benzoxazin-6-yl]-2-methoxy-3-pyridinyl]-4-fluoro- | [Molecular Formula]
C27H22FN3O6S | [MOL File]
2361215-32-7.mol | [Molecular Weight]
535.55 |
| Chemical Properties | Back Directory | [Boiling point ]
791.8±70.0 °C(Predicted) | [density ]
1.413±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [form ]
Solid | [pka]
6.79±0.40(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Description]
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 IC50 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[1]. PI3K/mTOR Inhibitor-4 (compound 8d-1) has enzymatic inhibition activity for PI3Kα, PI3Kδ, mTOR, PI3Kβ and PI3Kγ with IC50 values of 0.63 nM, 9.2 nM, 13.85 nM, 94.54 nM and 22 nM, respectively[1].
PI3K/mTOR Inhibitor-4 shows potent anti-proliferation activity in A549, Hela, HCT-116, HepG2, A375 and MCF-7 cells with IC50 values of 1.35 nM, 1.22 nM, 13.44 nM, 1.08 nM, 18.4 nM and 8.26 nM, respectively[1].
PI3K/mTOR Inhibitor-4 (2.5-10 µM; 24 h) inhibits the PI3K/AKT/mTOR pathway[1]. Cell Viability Assay[1] Western Blot Analysis[1] PI3K/mTOR Inhibitor-4 (compound 8d-1) (i.v., oral; 1mg/kg, 10 mg/kg) displays favorable pharmacokinetic parameters in Sprague-Dawley rats[1].
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[1]. | [Uses]
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 IC50 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[1]. | [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[1].
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[1]. | Animal Model: | SD rats (male; 200-220 g)[1] | | Dosage: | 1, 10 mg/kg | | Administration: | Intravenous, oral | | Result: | | IV (1 mg/kg) | PO (10 mg/kg) | | CL (ml/min/kg) | Vss (ml/kg) | Tmax (h) | Cmax (ng/ml) | AUCinf (ng*h/ml) | t1/2 (h) | F(%) | | 8.6 | 1199.81 | 2.67 | 886.67 | 4753.35 | 1.78 | 24.1 |
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| Animal Model: | BALB/c nude mice (female; 6-7 weeks; 18-22 g)[1] | | 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. |
| [IC 50]
PI3Kα: 0.63 nM (IC50); PI3Kδ: 9.2 nM (IC50); mTOR: 13.85 nM (IC50); PI3Kβ: 94.54 nM (IC50); PI3Kγ: 22 nM (IC50) | [References]
[1] Guoyi Yan, et al. Discovery of 4-phenyl-2H-benzo[b][1,4]oxazin-3(4H)-one derivatives as potent and orally active PI3K/mTOR dual inhibitors. Eur J Med Chem DOI:10.1016/j.ejmech.2019.06.021 |
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