6-{difluoro[6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl]methyl}quinoline

• ChemBase编号: 72520
• 分子式: C19H13F2N7
• 平均质量: 377.3502264
• 单一同位素质量: 377.12004989
• SMILES: n1cccc2c1ccc(c2)C(c1n2c(nn1)ccc(n2)c1cnn(c1)C)(F)F
• Canonical SMILES: Cn1ncc(c1)c1ccc2n(n1)c(nn2)C(c1ccc2c(c1)cccn2)(F)F
• InChI: InChI=1S/C19H13F2N7/c1-27-11-13(10-23-27)16-6-7-17-24-25-18(28(17)26-16)19(20,21)14-4-5-15-12(9-14)3-2-8-22-15/h2-11H,1H3
• InChIKey: JRWCBEOAFGHNNU-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: 6-{difluoro[6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl]methyl}quinoline
• IUPAC传统名: 6-{difluoro[6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl]methyl}quinoline
• 别名: JNJ-38877605

登记号

• CAS号: 943540-75-8
• PubChem SID: 162037445
• PubChem CID: 46911863

理论计算性质

• 质子受体: 5
• 质子供体: 0
• LogD (pH = 5.5): 3.0044818
• LogD (pH = 7.4): 3.0361044
• Log P: 3.0365243
• 摩尔折射率: 120.8601 cm^3
• 极化性: 38.454155 Å^3
• 极化表面积: 73.79 Å^2
• 可自由旋转的化学键: 3
• 里宾斯基五规则: true

分子性质

理化性质

• 溶解度: DMSO

安全信息

• 保存条件: -20°C

药理学性质

• 作用靶点: c-Met

产品相关信息

• 成盐信息: Free Base

详细说明

Selleck Chemicals - S1114

Research Area

• Description: Cancer

Biological Activity

• Description: JNJ-38877605 is an ATP-competitive inhibitor of c-Met with IC50 of 4 nM.
• Targets: c-Met
• IC50: 4 nM ^[1]
• In Vitro: JNJ-38877605 shows more than 600-fold selectivity for c-Met compared with more than 200 other diverse tyrosine and serine-threonine kinases and also potently inhibits HGF-stimulated and constitutively activated c-Met phosphorylation in vitro. ^[1] In EBC1, GTL16, NCI-H1993, and MKN45 cells, JNJ-38877605 (500 nM) leads to a significant reduction of phosphorylation of Met and RON, another key player in invasive growth. ^[2] A recent study shows that JNJ-38877605 is involved in modulating secretion of IL-8, GROa, uPAR and IL-6 in GTL16 cells. ^[3]
• In Vivo: In mice bearing established GTL16 xenografts, JNJ-38877605, dosed orally with 40 mg/kg/day for 72 hours, results in a statistically significant decrease in the plasma levels of human IL-8 (from 0.150 ng/mL to 0.050 ng/mL) and GROα (from 0.080 ng/mL to 0.030 ng/mL). While concentrations of uPAR in the blood become reduced to more than 50% at the same dose. ^[3]
• Clinical Trials: JNJ-38877605 is currently in Phase I clinical trials in patients with Neoplasms.

Protocol

• Protocol: Animal Study ^[3]
• Animal Models: GTL16 cells are inoculated subcutaneously into the right posterior flank (or both right and left posterior flanks, for determination of uPAR and IL-6) of 6-week-old immunodeficient nu/nu female mice on Swiss CD1 background.
• Formulation: JNJ-38877605 is dissolved in PBS.
• Doses: ≤40 mg/kg/day
• Administration: Administered via p.o.

References

• References: [1] Perera T, et al. Presented at the 99th AACR Annual Meeting; 2008 Apr 12-16; San Diego (CA): Abst
• References: [2] De Bacco F, et al. J Natl Cancer Inst. 2011 Apr, 103(8), 645-661.
• References: [3] Torti D, et al. Int J Cancer. 2012, 130(6), 1357-1366.

参考文献

• Perera T, et al. Presented at the 99th AACR Annual Meeting; 2008 Apr 12-16; San Diego (CA): Abst
• De Bacco F, et al. J Natl Cancer Inst. 2011 Apr, 103(8), 645-661.
• Torti D, et al. Int J Cancer. 2012, 130(6), 1357-1366.