mitogen-activated protein kinase kinase 2 | STE7 family | IUPHAR/BPS Guide to PHARMACOLOGY

mitogen-activated protein kinase kinase 2

Target id: 2063

Nomenclature: mitogen-activated protein kinase kinase 2

Abbreviated Name: MEK2

Family: STE7 family

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for mitogen-activated protein kinase kinase 2 in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 400 19p13.3 MAP2K2 mitogen-activated protein kinase kinase 2
Mouse - 401 10 C1 Map2k2 mitogen-activated protein kinase kinase 2
Rat - 400 7 q11 Map2k2 mitogen activated protein kinase kinase 2
Previous and Unofficial Names
ERK activator kinase 2 | MAP kinase kinase 2 | MKK2 | PRKMK2 | dual specificity mitogen-activated protein kinase kinase 2
Database Links
BRENDA
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  X-ray structure of the human mitogen-activated protein kinase kinase 2 (MEK2)in a complex with ligand and MgATP
PDB Id:  1S9I
Resolution:  3.2Å
Species:  Human
References:  5
Enzyme Reaction
EC Number: 2.7.12.2

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
trametinib Hs Inhibition 8.7 pIC50 10
pIC50 8.7 (IC50 1.8x10-9 M) [10]
voruciclib Hs Inhibition 7.1 pIC50 6
pIC50 7.1 (IC50 8.7x10-8 M) [6]
MEK1/2 inhibitor Hs Inhibition 6.7 pIC50 3
pIC50 6.7 (IC50 2.2x10-7 M) [3]
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
binimetinib Hs Negative 7.9 pIC50 7
pIC50 7.9 (IC50 1.2x10-8 M) [7]
refametinib Hs Negative 7.3 pIC50 4
pIC50 7.3 (IC50 4.7x10-8 M) [4]
cobimetinib Hs Negative 6.7 pIC50 8
pIC50 6.7 (IC50 1.99x10-7 M) [8]
DiscoveRx KINOMEscan® screen
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 2,9

Key to terms and symbols Click column headers to sort
Target used in screen: MEK2
Ligand Sp. Type Action Affinity Units
lestaurtinib Hs Inhibitor Inhibition 8.4 pKd
bosutinib Hs Inhibitor Inhibition 8.0 pKd
foretinib Hs Inhibitor Inhibition 7.9 pKd
neratinib Hs Inhibitor Inhibition 7.6 pKd
staurosporine Hs Inhibitor Inhibition 7.6 pKd
sunitinib Hs Inhibitor Inhibition 7.0 pKd
SU-14813 Hs Inhibitor Inhibition 6.9 pKd
PP-242 Hs Inhibitor Inhibition 6.7 pKd
dovitinib Hs Inhibitor Inhibition 6.5 pKd
CI-1040 Hs Inhibitor Inhibition 6.4 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.

A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform.

http://www.millipore.com/techpublications/tech1/pf3036
http://www.reactionbiology.com/webapps/main/pages/kinase.aspx


Reference: ...1

Key to terms and symbols Click column headers to sort
Target used in screen: nd/MEK2
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
bosutinib Hs Inhibitor Inhibition 8.4
staurosporine Hs Inhibitor Inhibition 8.4
K-252a Hs Inhibitor Inhibition 16.2
sunitinib Hs Inhibitor Inhibition 25.4
SU11652 Hs Inhibitor Inhibition 41.4
dovitinib Hs Inhibitor Inhibition 43.0
PD98059 Hs Inhibitor Inhibition 69.2
PD 169316 Hs Inhibitor Inhibition 71.7
GSK-3beta inhibitor VIII Hs Inhibitor Inhibition 73.5
JNK inhibitor V Hs Inhibitor Inhibition 76.2
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
Disease:  Cardiofaciocutaneous syndrome 4; CFC4
Synonyms: Cardiofaciocutaneous syndrome [Orphanet: ORPHA1340]
OMIM: 615280
Orphanet: ORPHA1340

References

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1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat. Biotechnol., 29 (11): 1039-45. [PMID:22037377]

2. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat. Biotechnol., 29 (11): 1046-51. [PMID:22037378]

3. Fedorov O, Marsden B, Pogacic V, Rellos P, Müller S, Bullock AN, Schwaller J, Sundström M, Knapp S. (2007) A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc. Natl. Acad. Sci. U.S.A., 104 (51): 20523-8. [PMID:18077363]

4. Iverson C, Larson G, Lai C, Yeh LT, Dadson C, Weingarten P, Appleby T, Vo T, Maderna A, Vernier JM et al.. (2009) RDEA119/BAY 869766: a potent, selective, allosteric inhibitor of MEK1/2 for the treatment of cancer. Cancer Res., 69 (17): 6839-47. [PMID:19706763]

5. Ohren JF, Chen H, Pavlovsky A, Whitehead C, Zhang E, Kuffa P, Yan C, McConnell P, Spessard C, Banotai C et al.. (2004) Structures of human MAP kinase kinase 1 (MEK1) and MEK2 describe novel noncompetitive kinase inhibition. Nat. Struct. Mol. Biol., 11 (12): 1192-7. [PMID:15543157]

6. Paiva C, Godbersen JC, Soderquist RS, Rowland T, Kilmarx S, Spurgeon SE, Brown JR, Srinivasa SP, Danilov AV. (2015) Cyclin-Dependent Kinase Inhibitor P1446A Induces Apoptosis in a JNK/p38 MAPK-Dependent Manner in Chronic Lymphocytic Leukemia B-Cells. PLoS ONE, 10 (11): e0143685. [PMID:26606677]

7. Pheneger J, Wallace, E, Marlow, A Hurley B, Lyssikatos J, Bendele AM, Lee PA. (2006) Characterization of ARRY-438162, a Potent MEK Inhibitor in Combination with Methotrexate or Ibuprofen in In Vivo Models of Arthritis.[abstract]. American College of Rheumatology. 2006 Annual Scientific Meeting.,: Abstract 794.

8. Rice KD, Aay N, Anand NK, Blazey CM, Bowles OJ, Bussenius J, Costanzo S, Curtis JK, Defina SC, Dubenko L et al.. (2012) Novel Carboxamide-Based Allosteric MEK Inhibitors: Discovery and Optimization Efforts toward XL518 (GDC-0973). ACS Med. Che. Letters, 3 (5): 416–421.

9. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem. Biol., 17 (11): 1241-9. [PMID:21095574]

10. Yamaguchi T, Kakefuda R, Tajima N, Sowa Y, Sakai T. (2011) Antitumor activities of JTP-74057 (GSK1120212), a novel MEK1/2 inhibitor, on colorectal cancer cell lines in vitro and in vivo. Int. J. Oncol., 39 (1): 23-31. [PMID:21523318]

How to cite this page

STE7 family: mitogen-activated protein kinase kinase 2. Last modified on 25/04/2018. Accessed on 17/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2063.