Selumetinib
Selumetinib : Covalent, ATP noncompetitive inhibitor of MAP2K1
Structure
In Cells
In Model Organisms
SERP ratings and comments
SERP Ratings
(last updated: 12 Jun 2016 )
SERP Ratings
SERP Comments:
Selumetinib has anti-proliferative activity in cell line harboring B-RAF and RAS mutations and inhibits MEK1/2 (14 nM). It is relatively selective when tested against a panel of kinases, and commercially available from many sources.
(last updated: 23 Jun 2016 )
SERP Ratings
SERP Comments:
This probe is an allosteric, non-ATP competitive and selective inhibitor of MEK1/2 kinase, a component of RAS-RAF-MEK-ERK growth pathway. It displays a remarkable selectivity for MEK1/2 with IC50 14 nM. It does not inhibit a range of other kinases at 10 uM concentration such as p38 alpha, EGFR, B-RAF, c-SRC and others. The compound does not inhibit phosphorylation of MEK1/2 by RAF yet inhibits phosphorylation of downstream ERK. Cell lines with V600E B-RAF mutation are the most sensitive to this compound. This inhibitor is orally bioavailable and inhibits tumor xenografts in mice at 10-100 mg/kg doses. This inhibitor is highly recommended for cell-based studies in combination with an ATP-competitive MEK inhibitor. The use of this probe to interrogate the role of MEK in vivo is not recommended because there are no data about tissue and organ distribution of the probe upon its administration to animals, and effect on MAPK pathway were not provided.
(last updated: 27 Jun 2016 )