Description
AZD6244(Selumetinib) can inhibit MEK with IC50 of 14 nM.
Storage
2 years at -20centigrade Powder
Molecular Formula
C17H15BrClFN4O3
Chemical Name
6-(4-bromo-2-chlorophenylamino)-7-fluoro-N-(2-hydroxyethoxy)-3-methyl-3H-benzo[d]imidazole-5-carboxamide
Solubility
DMSO 92 mg/mL Water
In vitro
As a potent, selective, and ATP-uncompetitive inhibitor of MAPK/ERK kinase 1/2, AZD6244 (Selumetinib, ARRY-142886) is highly potent to inhibit MEK1 with IC50 of 14 nM. AZD6244 inhibits the MEK-ERK pathway across a spectrum of thyroid cancer cells. MEK inhibition is cytostatic in papillary thyroid cancer and anaplastic thyroid cancer cells bearing a BRAF mutation and may have less impact on thyroid cancer cells lacking this mutation. AZD6244 potently inhibited MEK 1/2 activity in thyroid cancer cell lines regardless of BRAF mutation status, as evidenced by reduced ERK phosphorylation. Four BRAF mutant lines exhibited growth inhibition at low doses of the drug, with GI50 concentrations ranging from 14 to 50 nm, predominantly via a G0/G1 arrest, comparable with findings in a sensitive BRAF mutant melanoma cell line.
In vivo
Nude mouse xenograft tumors derived from the BRAF mutant line ARO exhibited dose-dependent growth inhibition by AZD6244, with effective treatment at 10 mg/kg by oral gavage. This effect was primarily cytostatic and associated with marked inhibition of ERK phosphorylation.
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