Product Description

AZD-6244 (Selumetinib) is an orally-available, aminobenzimidazole-based, allosteric inhibitor of MEK1 kinase with an IC50 of 14 nM. [1] IC50 concentrations of <40 nM were observed in cellular phosphorylation assays measuring ERK1/2 in various cell lines. In cellular growth assays, AZD-6244 was more potent in cell lines containing activating B-Raf and Ras mutations, with IC50 values ranging from 59 to 473 nM. In HT-29 and Malme-3M cell studies, AZD-6244 was found to induce G1-S cell cycle arrest, inducing apoptosis after a 2-day incubation period. [1] In Colo-205 xenografts, AZD6244 induced increased levels of cleaved caspase-3, indicating apoptosis. [2]In diffuse large B-cell lymphoma (DLBCL) lines, nanomolar concentration of AZD-6244 effectively downregulated MEK/ERK target substrates, including c-Myc, Mcl-1, and Bcl-2. [3]

Technical information:

Chemical Formula: C17H15BrClFN4O3
CAS #: 606143-52-6
Molecular Weight: 457.68
Purity: >98%
Appearance: White
Chemical Name: 6-(4-bromo-2-chlorophenylamino)-7-fluoro-N-(2-hydroxyethoxy)-3-methyl-3H-benzo[d]imidazole-5-carboxamide
Solubility: Up to 100 mM in DMSO
Synonyms: AZD-6244, AZD 6244, AZD6244, Selumetinib, Selumetinib sulfate, NSC-748727, ARRY-142886

Shipping Condition: The product is shipped in a glass vial at ambient temperature. Storage condition: For longer shelf life, store solid powder at 4oC desiccated, or store DMSO solution at -20oC.

Reference:

1. Yeh et al., Biological characterization of ARRY-142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1/2 inhibitor. Clin. Cancer Res. 2007, 13, 1576-1583 Pubmed ID: 17332304
2. Davies et al., AZD6244 (ARRY-142886), a potent inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 kinases: mechanism of action in vivo, pharmacokinetic/pharmacodynamic relationship, and potential for combination in preclinical models. Mol. Cancer Ther. 2007, 6, 2209-2219. Pubmed ID: 17699718
3. Bhalla et al., The novel anti-MEK small molecule AZD6244 induces BIM-dependent and AKT-independent apoptosis in diffuse large B-cell lymphoma. Blood, 2011, 118(4), 1052-1061. Pubmed ID: 21628402