Selumetinib

Reagent Authentication Certificate:

Chemical Probes Portal Selumetinib.pdf

Protein target name:

MAP2K1

Mechanism of action:

CovalentATP noncompetitive inhibitor

Recommended Concentration for use in cells:

10 nM - 200 nM

Probe Availability

Abcam (606143-52-6)

Cayman (606143-52-6)

MedChem Express (606143-52-6)

Probe Information

Target and Probe Information

Target Details

Target class:

Protein kinase

Subclass:

STE

HUGO ID:

HGNC:6840

Entrez gene ID:

5604

UNIPROT ID:

Q02750

Target alias:

CFC3, MAPKK1, MEK1, MKK1, PRKMK1

Probe Details

Chemical Probes Portal ID:

CPP99

Probe alias:

606143-52-6, AZD6244, AZD 6244, AZD-6244, ARRY-142886

PubChem CID:

10127622

ChEMBL ID:

CHEMBL1614701

SMILES string:

CN1C=NC2=C1C=C(C(=C2F)NC3=C(C=C(C=C3)Br)Cl)C(=O)NOCCO

InChi Key:

CYOHGALHFOKKQC-UHFFFAOYSA-N

Orthogonal probe:

Trametinib

PAINs evaluation:

PAINs free

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

14 nM

Potency assay:

Radiometric kinase assay

Off target activity

Potency assay (off target):

No activity was detected with 10 uM Selumetinib against 40 kinases.

In cell validation

On target activity in cells

Potency in cells:

IC50

10 nM

Potency assay (cells):

Inhibition of substrate phosphorylation in Malme-3M cells

Target engagement assay (cells):

Indirect: inhibition of substrate phosphorylation

In vivo validation

Organism:

nude mice

Dose:

10-100 mg/kg

Route of delivery:

Oral

Organ of Interest

Organ (O):

xenograft

Target engagement assay:

Indirect: inhibition of substrate phosphorylation in xenograft tissue

Primary Reference

Reference (doi):

10.1158/1078-0432.CCR-06-1150

Reference (PMID):

17332304

External Resources

Available data:

GDSC1 GDSC1 GDSC2

Endorsed probe

The Chemical Probes Portal endorses this compound as chemical probe for use in cells and in model organisms.

SAB Rating

Rating for use in Cells

3 review(s)

Rating for use in Model Organisms

3 review(s)

SAB Members

SAB 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.

Jun 30 2016 - 12:41am

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.

Jun 30 2016 - 12:41am

Selumetinib

Probe Availability

Probe Information

Target Details

CFC3, MAPKK1, MEK1, MKK1, PRKMK1

Probe Details

In vitro validation

In cell validation

In vivo validation

Primary Reference

External Resources

Supporting Organizations

Interested in supporting the portal?

Search form

Selumetinib

Probe Availability

Probe Information

Target Details

CFC3, MAPKK1, MEK1, MKK1, PRKMK1

Probe Details

In vitro validation

In cell validation

In vivo validation

Primary Reference

External Resources

Supporting Organizations

Interested in supporting the portal?