5-[(4-bromo-2-chlorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-1,3-benzodiazole-6-carboxamide

• ChemBase编号: 72456
• 分子式: C17H15BrClFN4O3
• 平均质量: 457.6814032
• 单一同位素质量: 456.00000826
• SMILES: c1c2c(c(c(c1C(=O)NOCCO)Nc1ccc(cc1Cl)Br)F)ncn2C
• Canonical SMILES: OCCONC(=O)c1cc2n(C)cnc2c(c1Nc1ccc(cc1Cl)Br)F
• InChI: InChI=1S/C17H15BrClFN4O3/c1-24-8-21-16-13(24)7-10(17(26)23-27-5-4-25)15(14(16)20)22-12-3-2-9(18)6-11(12)19/h2-3,6-8,22,25H,4-5H2,1H3,(H,23,26)
• InChIKey: CYOHGALHFOKKQC-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: 5-[(4-bromo-2-chlorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-1,3-benzodiazole-6-carboxamide
• IUPAC传统名: selumetinib
• 别名: ARRY-142886; Selumetinib; AZD6244(Selumetinib); 5-[(4-Bromo-2-chlorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzimidazole-6-carboxamide; 5-[(4-Bromo-2-chlorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzimidazole-6-carboxamide; ARRY 142886; AZD 6244; Selumetinib; 5-((4-bromo-2-chlorophenyl)amino)-4-fluoro-n-(2-hydroxyethoxy)-1-methyl-1h-benzimidazole-6-carboxamide

登记号

• CAS号: 606143-52-6
• PubChem SID: 162037381
• PubChem CID: 10127622

理论计算性质

• Acid pKa: 10.265881
• 质子受体: 5
• 质子供体: 3
• LogD (pH = 5.5): 4.086982
• LogD (pH = 7.4): 4.2702503
• Log P: 4.2739224
• 摩尔折射率: 102.613 cm^3
• 极化性: 39.50163 Å^3
• 极化表面积: 88.41 Å^2
• 可自由旋转的化学键: 6
• 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: MEK

产品相关信息

• 纯度: 95+%; 97%
• 成盐信息: Free Base

详细说明

Selleck Chemicals - S1008

Research Area

• Description: Cancer

Protocol

• Protocol: Kinase Assay ^[1]
• Assay of MEK Kinase Activity: Anti-MEK1 antibody is used to immunoprecipitate MEK1 molecules. MEK kinase activity is measured as the ability of immuno-isolated MEK1 to activate recombinant ERK1 in a coupled assay using MBP as the end point of the assay. Phosphorylated MBP is resolved on a 14% SDS-PAGE gel and vacuum-dried before exposure to X-ray film.
• Protocol: Cell Assay ^[1]
• Cell Lines: Primary HCC cell lines including 2-1318, 4-1318 and 26-1004 cells
• Concentrations: ~ 10 μM
• Incubation Time: 24 or 48 hours
• Methods: Cells are seeded at a density of 2.0 × 10^4. After 48 hours incubation, the cells are rinsed twice with culture media. Cells are treated with various concentrations of AZD6244 for 24 or 48 hours. Cell viability is determined by the 3-(4,5-dimethylthiazol-2y1)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell proliferation is assayed using a bromodeoxyuridine kit.
• Protocol: Animal Study ^[1]
• Animal Models: HCC xenografts in mice homozygous for the SCID (severe combined immunodeficiency) mutation
• Formulation: In water
• Doses: 50 or 100mg/kg
• Administration: Administered via p.o.

References

• References: [1] Huynh H, et al, Mol Cancer Therapy, 2007, 6 (1), 138-146
• References: [2] Garon EB, et al, Mol Cancer Thera, 2010, 9 (7), 1985-1994.
• References: [3] Yeh TC, et al, Clin Cancer Res, 2007, 13 (5), 1576-1583.
• References: [4] Huynh H, et al, Mol Cancer Ther, 2007, 6 (9), 2468-2476.
• References: [5] Davies BR, et al. Mol Cancer Ther, 2007, 6(8), 2209-2219.
• References: [6] Morelli MP, et al. Clin Cancer Res, 2012, 18(4), 1051-1062.
• References: [7] Yuen JS, et al. Int J Oncol, 2012, 41(2), 712-720.

Toronto Research Chemicals - S254000

It is a tight-binding, uncompetitive inhibitor of mitogen-activated protein kinase kinases (MEK) 1 and 2 currently in clinical development. It is useful as biomarker in human lung cancer cell.

参考文献

• Huynh H, et al, Mol Cancer Ther, 2007, 6 (9), 2468-2476.
• Davies BR, et al. Mol Cancer Ther, 2007, 6(8), 2209-2219.
• Morelli MP, et al. Clin Cancer Res, 2012, 18(4), 1051-1062.
• Huynh H, et al, Mol Cancer Therapy, 2007, 6 (1), 138-146
• Garon EB, et al, Mol Cancer Thera, 2010, 9 (7), 1985-1994.
• Yeh TC, et al, Clin Cancer Res, 2007, 13 (5), 1576-1583.
• Yuen JS, et al. Int J Oncol, 2012, 41(2), 712-720.
• Ciardiello, F., et al.: Clin. Cancer Res., 7, 1459 (2001)
• Hidalgo, M., et al.: J. Clin. Oncol., 19, 3267 (2001)