中文名 | GNF-7 |
英文名 | BenzaMide, N-[3-[1,4-dihydro-1-Methyl-7-[(6-Methyl-3-pyridinyl)aMino]-2-oxopyriMido[4,5-d]pyriMidin-3(2H)-yl]-4-Methylphenyl]-3-(trifluoroMethyl)- |
别名 | 化合物GNF7 BCR-ABL WT和BCR-ABL T315I抑制剂(GNF-7) N-[3-[1,4-二氢-1-甲基-7-[(6-甲基-3-吡啶基)氨基]-2-氧代嘧啶并[4,5-D]嘧啶-3(2H)-基]-4-甲基苯基]-3-(三氟甲基)苯甲酰胺 |
英文别名 | GNF-7 CS-1945 BenzaMide, N-[3-[1,4-dihy... N-[4-methyl-3-[1-methyl-7-[(6-methylpyridin-3-yl)amino]-2-oxo-4H-pyrimido[4,5-d]pyrimidin-3-yl]phenyl]-3-(trifluoromethyl)benzamide N-[3-[1,4-Dihydro-1-methyl-7-[(6-methyl-3-pyridinyl)amino]-2-oxopyrimido[4,5-d]pyrimidin-3(2H)-yl]-4-methylphenyl]-3-(trifluoromethyl)benzamide N-(4-Methyl-3-(1-methyl-7-((6-methylpyridin-3-yl)amino)-2-oxo-1,2-dihydropyrimido[4,5-d]pyrimidin-3(4H)-yl)phenyl)-3-(trifluoromethyl)benzamide BenzaMide, N-[3-[1,4-dihydro-1-Methyl-7-[(6-Methyl-3-pyridinyl)aMino]-2-oxopyriMido[4,5-d]pyriMidin-3(2H)-yl]-4-Methylphenyl]-3-(trifluoroMethyl)- |
CAS | 839706-07-9 |
化学式 | C28H24F3N7O2 |
分子量 | 547.53 |
密度 | 1.404±0.06 g/cm3(Predicted) |
酸度系数 | 12.82±0.70(Predicted) |
存储条件 | 2-8℃ |
体外研究 | GNF-7 potently inhibits wild-type Bcr-Abl (IC 50 <5 nM) and Bcr-Abl mutants such as T315I (IC 50 =11 nM), G250E (IC 50 <5 nM), E255V (IC 50 =10 nM), F317L (IC 50 <5 nM) and M351T (IC 50 <5 nM) in cellular assays. GNF-7 (1 μM; 2 hours) suppresses AKT/mTOR signaling and GCK downstream. GNF-7 (1 μM; 24 hours) induces of apoptosis and cell cycle arrest in NRAS mutant cell lines. Western Blot Analysis Cell Line: Ba/F3-NRAS-G12D cells, OCI-AML3 cells Concentration: 1 μM Incubation Time: 2 hours Result: Caused a decreased level of phosphorylation of p70S6K1, AKT (S473), JNK, and p38. Apoptosis Analysis Cell Line: OCI-AML3 cells Concentration: 1 μM Incubation Time: 24 hours Result: Increased the levels of both cleaved PARP and cleaved caspase 3 and diminished bcl-2 and MCL1. Cell Cycle Analysis Cell Line: OCI-AML3 cells Concentration: 1 μM Incubation Time: 24 hours Result: Induced of G0-G1 arrest. |
体内研究 | GNF-7 (10-20 mg/kg; o.p.; daily; for 7 days) displays significant in vivo efficacy against T315I Bcr-Abl in the bioluminescent xenograft mouse model. GNF-7 exhibits moderate oral bioavailability (mice 36%) and C max (mice 3616 nM) following oral administration (mice 20 mg/kg). GNF-7 exhibits terminal elimination half-lives (mice 3.8 h) due to high plasma clearance (8.6 mL/min/kg) following intravenous injection (mice 5 mg/kg). Animal Model: 6-8 weeks old SCID beige female mice, with Ba/F3-T315I-Bcr-Abl cells xenograft Dosage: 10 mg/kg, 20 mg/kg Administration: Oral administration, daily, for 7 days Result: Effectively inhibited tumor growth of T315I-Bcr-Abl-Ba/F3 cells in mice at low doses (10 mg/kg). Animal Model: 5-6 weeks old male Balb/c mice (20-25 g) Dosage: 5 mg/kg for i.v.; 20 mg/kg for i.g. (Pharmacokinetic Analysis) Administration: Intravenous injection and oral gavage Result: Oral bioavailability (36%), C max (3616 nM), T 1/2 (3.2 h). |
上游原料 | 5-羟甲基脲嘧啶 |
1mg | 5mg | 10mg | |
---|---|---|---|
1 mM | 1.826 ml | 9.132 ml | 18.264 ml |
5 mM | 0.365 ml | 1.826 ml | 3.653 ml |
10 mM | 0.183 ml | 0.913 ml | 1.826 ml |
5 mM | 0.037 ml | 0.183 ml | 0.365 ml |
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