Selumetinib

Covalent, ATP noncompetitive inhibitor of MAP2K1

Structure

Information

Protein target names: MAP2K1

Mechanism of action: Covalent, ATP noncompetitive inhibitor

Recommended in-cell concentration:
10 nM - 200 nM

In Vitro Validations

Uniprot ID: Q02750
Target Class: Kinase
Target SubClass: STE
Potency: IC50
Potency Value: 14 nM
Potency Assay: Radiometric kinase assay
PDB ID for probe-target interaction (3D structure): --
Target aliases:
Dual specificity mitogen-activated protein kinase ...

DOI Reference: 10.1158/1078-0432.CCR-06-1150

In Cell Validations

In Vivo Data

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SERP ratings and comments


SERP Ratings

In Cell Rating
In Model Organisms

(last updated: 12 Jun 2016 )

SERP Ratings

In Cell Rating
In Model Organisms

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

In Cell Rating
In Model Organisms

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 )