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mitogen-activated protein kinase kinase 7

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Target not currently curated in GtoImmuPdb

Target id: 2068

Nomenclature: mitogen-activated protein kinase kinase 7

Abbreviated Name: MKK7

Family: STE7 family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 419 19p13.2 MAP2K7 mitogen-activated protein kinase kinase 7
Mouse - 535 8 A1.1 Map2k7 mitogen-activated protein kinase kinase 7
Rat - 419 12p12 Map2k7 mitogen activated protein kinase kinase 7
Gene and Protein Information Comments
Multiple alternatively spliced transcript variants encoding distinct isoforms have been found, but only the transcript variant generating the 419 amino acid protein has been supported and defined. Isoform B is postulated to contain a 43 amino acid insertion, translating to a 462 amino acid protein.
Previous and Unofficial Names Click here for help
c-Jun N-terminal kinase kinase 2 | dual specificity mitogen-activated protein kinase kinase 7 | JNK kinase 2 | JNKK2 | MAP kinase kinase 7 | MKK7 | PRKMK7 | SAPKK4 | sek2 | SKK4 | Stress-activated protein kinase kinase 4
Database Links Click here for help
Alphafold O14733 (Hs), Q8CE90 (Mm), Q4KSH7 (Rn)
BRENDA 2.7.12.2
ChEMBL Target CHEMBL3530 (Hs), CHEMBL4523385 (Mm)
Ensembl Gene ENSG00000076984 (Hs), ENSMUSG00000002948 (Mm), ENSRNOG00000001047 (Rn)
Entrez Gene 5609 (Hs), 26400 (Mm), 363855 (Rn)
Human Protein Atlas ENSG00000076984 (Hs)
KEGG Enzyme 2.7.12.2
KEGG Gene hsa:5609 (Hs), mmu:26400 (Mm), rno:363855 (Rn)
OMIM 603014 (Hs)
Pharos O14733 (Hs)
RefSeq Nucleotide NM_145185 (Hs), NM_011944 (Mm), NM_001025425 (Rn)
RefSeq Protein NP_660186 (Hs), NP_036074 (Mm), NP_001020596 (Rn)
UniProtKB O14733 (Hs), Q8CE90 (Mm), Q4KSH7 (Rn)
Wikipedia MAP2K7 (Hs)
Enzyme Reaction Click here for help
EC Number: 2.7.12.2

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 1k [PMID: 35912476] Small molecule or natural product Hs Inhibition 8.4 pIC50 3
⤷ pIC50 8.4 (IC50 4x10-9 M) [3]
Description: Determined in an in vitro kinase activity assay
compound 11 [PMID: 26431428] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.3 pIC50 4
⤷ pIC50 5.3 (IC50 5x10-6 M) [4]
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
cobimetinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Negative <5.0 pIC50 5
⤷ pIC50 <5.0 (IC50 >1x10-5 M) [5]
DiscoveRx KINOMEscan® screen Click here for help
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: 1,6
Key to terms and symbols Click column headers to sort
Target used in screen: MKK7
Ligand Sp. Type Action Value Parameter
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 7.6 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.5 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.1 pKd
canertinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 7.0 pKd
neratinib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 6.3 pKd
SB203580 Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition <5.5 pKd
ruboxistaurin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition <5.5 pKd
erlotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition <5.5 pKd
linifanib Small molecule or natural product Hs Inhibitor Inhibition <5.5 pKd
GSK690693 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition <5.5 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen Click here for help
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: 2...
Key to terms and symbols Click column headers to sort
Target used in screen: MKK7β/nd
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
K-252a Small molecule or natural product Hs Inhibitor Inhibition 7.0 0.0
JNK inhibitor VIII Small molecule or natural product Hs Inhibitor Inhibition 11.0 4.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 11.0 1.5
isogranulatimide Small molecule or natural product Hs Inhibitor Inhibition 42.0 27.0
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 43.0 12.0
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 52.0 34.0
indirubin-3'-monoxime Small molecule or natural product Hs Inhibitor Inhibition 52.0 7.0
indirubin derivative E804 Small molecule or natural product Hs Inhibitor Inhibition 54.0 5.0
Cdk2 inhibitor IV Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 56.0 16.0
SP600125 Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 58.0 6.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Cellular signalling
Immuno Process:  Immune regulation
Immuno Process:  Cytokine production & signalling

References

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1. 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]

2. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem J, 451 (2): 313-28. [PMID:23398362]

3. Gehrtz P, Marom S, Bührmann M, Hardick J, Kleinbölting S, Shraga A, Dubiella C, Gabizon R, Wiese JN, Müller MP et al.. (2022) Optimization of Covalent MKK7 Inhibitors via Crude Nanomole-Scale Libraries. J Med Chem, 65 (15): 10341-10356. [PMID:35912476]

4. Patel S, Harris SF, Gibbons P, Deshmukh G, Gustafson A, Kellar T, Lin H, Liu X, Liu Y, Liu Y et al.. (2015) Scaffold-Hopping and Structure-Based Discovery of Potent, Selective, And Brain Penetrant N-(1H-Pyrazol-3-yl)pyridin-2-amine Inhibitors of Dual Leucine Zipper Kinase (DLK, MAP3K12). J Med Chem, 58 (20): 8182-99. [PMID:26431428]

5. 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 Chem Lett, 3 (5): 416-21. [PMID:24900486]

6. 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]

How to cite this page

STE7 family: mitogen-activated protein kinase kinase 7. Last modified on 03/08/2022. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2068.