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Description: Selumetinib (also known as AZD6244; ARRY-142886; Koselugo) is a novel, potent, highly selective and orally bioavailable small molecule MEK1 inhibitor with anticancer activity. It is an approved medication for the treatment of children with neurofibromatosis type I, a genetic disorder of the nervous system causing tumors to grow on nerves. Selumetinib inhibits MEK1 with an IC50 of 14 nM in cell-free assays, and also inhibits ERK1/2 phosphorylation with an IC50 of 10 nM, but shows no inhibition against p38α, MKK6, EGFR, ErbB2, ERK2, B-Raf, etc. It exhibits excellent anti-proliferative activity in vitro and high in vivo antitumor efficacy
References: Mol Cancer Ther. 2007 Jan;6(1):138-46; Clin Cancer Res. 2007 Mar 1;13(5):1576-83.
Product Catalog 2023
Guide to Product Handling
selumetinib; ARRY-142886; AZD6244; ARRY142886; ARRY 142886; AZD-6244; AZD 6244; ARRY886; ARRY-886; ARRY 886
Chemical Name: 6-[(4-bromo-2-chlorophenyl)amino]-7-fluoro-N-(2-hydroxyethoxy)-3-methylbenzimidazole-5-carboxamide
InChi Key: CYOHGALHFOKKQC-UHFFFAOYSA-N
InChi Code: 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)
SMILES Code: O=C(C1=C(NC2=CC=C(Br)C=C2Cl)C(F)=C3C(N(C)C=N3)=C1)NOCCO
Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2
In vitro activity: AZD6244 is not competitive with ATP and inactivates the ERK1/2 phosphorylation with IC50 concentrations below 40 nM. AZD6244 also inhibits the growth of primary HCC cells through inhibition of ERK1/2 and p90RSK phosphorylation, accompanied with elevation of the cleavage of caspase-3 and caspase-7, and cleaved poly(ADP)ribose polymerase. AZD6244 has little effects on the p38, c-Jun-NH2-kinase, phosphatidylinositol 3-kinase, and MEK5/ERK5 pathways. AZD6244 is sensitive to Raf mutations in breast cancer cell lines and Ras mutations in NSCLC cell lines.
Kinase Assay: 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.
Cell Assay: Cells (Primary HCC cell lines including 2-1318, 4-1318 and 26-1004 cells) are seeded at a density of 2.0 × 104. 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.
Mol Cancer Ther. 2007 Jan;6(1):138-46; Clin Cancer Res. 2007 Mar 1;13(5):1576-83.
Purity ≥98%
COA
MSDS
NMR
Structure of ARRY-142886 and its ability to inhibit enzymatic MEK1 activity. Clin Cancer Res. 2007 Mar 1;13(5):1576-83.
Inhibition of tumor growth and decreased tumor phospho-ERK1/2 levels in a mouse HT-29 xenograft model.
Inhibition of basal and induced ERK1/2 phosphorylation in human cancer cell lines and PBMCs. Clin Cancer Res. 2007 Mar 1;13(5):1576-83.
Tumor growth inhibition in the mouse BxPC3 xenograft model. Clin Cancer Res. 2007 Mar 1;13(5):1576-83.