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

• ChemBase ID: 72456
• Molecular Formular: C17H15BrClFN4O3
• Molecular Mass: 457.6814032
• Monoisotopic Mass: 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

NAMES AND DATABASE IDS

Names

• IUPAC name: 5-[(4-bromo-2-chlorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-1,3-benzodiazole-6-carboxamide
• IUPAC Traditional name: selumetinib
• Synonyms: 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

Database IDs

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

CALCULATED PROPERTIES

• Acid pKa: 10.265881
• H Acceptors: 5
• H Donor: 3
• LogD (pH = 5.5): 4.086982
• LogD (pH = 7.4): 4.2702503
• Log P: 4.2739224
• Molar Refractivity: 102.613 cm^3
• Polarizability: 39.50163 Å^3
• Polar Surface Area: 88.41 Å^2
• Rotatable Bonds: 6
• Lipinski's Rule of Five: true

PROPERTIES

Physical Property

• Solubility: DMSO

Safety Information

• Storage Condition: -20°C

Pharmacology Properties

• Target: MEK

Product Information

• Purity: 95+%; 97%
• Salt Data: Free Base

DETAILS

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.

REFERENCES

• 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)