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MAPK activated protein kinase 2

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Target id: 2094

Nomenclature: MAPK activated protein kinase 2

Abbreviated Name: MAPKAPK2

Family: MAPKAPK subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 400 1q32.1 MAPKAPK2 MAPK activated protein kinase 2
Mouse - 386 1 E4 Mapkapk2 MAP kinase-activated protein kinase 2
Rat - 386 13 q13 Mapkapk2 MAPK activated protein kinase 2
Previous and Unofficial Names Click here for help
MAPKAP kinase 2 | mitogen-activated protein kinase-activated protein kinase 2 | Rps6kc1
Database Links Click here for help
Alphafold P49137 (Hs), P49138 (Mm)
BRENDA 2.7.11.1
CATH/Gene3D 4.10.1170.10
ChEMBL Target CHEMBL2208 (Hs), CHEMBL4990 (Mm)
Ensembl Gene ENSG00000162889 (Hs), ENSMUSG00000016528 (Mm), ENSRNOG00000004726 (Rn)
Entrez Gene 9261 (Hs), 17164 (Mm), 289014 (Rn)
Human Protein Atlas ENSG00000162889 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:9261 (Hs), mmu:17164 (Mm), rno:289014 (Rn)
OMIM 602006 (Hs)
Pharos P49137 (Hs)
RefSeq Nucleotide NM_004759 (Hs), NM_008551 (Mm), NM_178102 (Rn)
RefSeq Protein NP_004750 (Hs), NP_032577 (Mm), NP_835203 (Rn)
SynPHARM 81673 (in complex with compound 16 [PMID: 17480064])
81069 (in complex with PF-3644022)
81068 (in complex with PF-3644022)
UniProtKB P49137 (Hs), P49138 (Mm)
Wikipedia MAPKAPK2 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of MAPKAP2
PDB Id:  1KWP
Resolution:  2.8Å
Species:  Human
References:  9
Image of receptor 3D structure from RCSB PDB
Description:  PROTEIN KINASE MK2 IN COMPLEX WITH AN INHIBITOR (CRYSTAL FORM-1, SOAKING)
PDB Id:  2jbo
Ligand:  compound 16 [PMID: 17480064]
Resolution:  301.0Å
Species:  Human
References:  6
Enzyme Reaction Click here for help
EC Number: 2.7.11.1

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
PF-3644022 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.5 pKi 10
⤷ pKi 8.5 (Ki 3x10-9 M) [10]
MK2a inhibitor Small molecule or natural product Primary target of this compound Hs Inhibition 6.5 pKi 4
⤷ pKi 6.5 (Ki 3.3x10-7 M) [4]
PF-3644022 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.3 pIC50 10
⤷ pIC50 8.3 (IC50 5.2x10-9 M) [10]
compound 16 [PMID: 17480064] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.1 pIC50 2
⤷ pIC50 8.1 (IC50 8.5x10-9 M) [2]
compound 16 [PMID: 18945615] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.3 pIC50 11
⤷ pIC50 7.3 (IC50 5.1x10-8 M) [11]
gamcemetinib Small molecule or natural product Immunopharmacology Ligand Hs Irreversible inhibition 6.8 pIC50 8
⤷ pIC50 6.8 (IC50 1.56x10-7 M) [8]
compound 8 [PMID: 17480064] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.8 pIC50 2
⤷ pIC50 6.8 (IC50 1.71x10-7 M) [2]
compound 33 [PMID: 19364658] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 6.4 pIC50 7
⤷ pIC50 6.4 (IC50 3.9x10-7 M) [7]
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: 3,12
Key to terms and symbols Click column headers to sort
Target used in screen: MAPKAPK2
Ligand Sp. Type Action Value Parameter
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.6 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.1 pKd
erlotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition <5.5 pKd
GSK690693 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition <5.5 pKd
ruboxistaurin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition <5.5 pKd
SB203580 Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition <5.5 pKd
masitinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition <5.5 pKd
A-674563 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition <5.5 pKd
linifanib Small molecule or natural product Hs Inhibitor Inhibition <5.5 pKd
gefitinib Small molecule or natural product Approved drug 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: 1,5
Key to terms and symbols Click column headers to sort
Target used in screen: MAPKAP-K2/MAPKAPK2
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 13.1 0.0 -6.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 40.4 8.0 -3.0
alsterpaullone Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 77.4 69.0 50.0
alsterpaullone 2-cyanoethyl Small molecule or natural product Hs Inhibitor Inhibition 83.4 57.0 39.0
GF109203X Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 85.4 108.0 73.0
AG 1296 Small molecule or natural product Hs Inhibitor Inhibition 85.9 101.0 80.0
dorsomorphin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 86.6 98.0 111.0
GSK-3 inhibitor IX Small molecule or natural product Hs Inhibitor Inhibition 86.9 96.0 90.0
PD 174265 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 87.1 88.0 95.0
aloisine Small molecule or natural product Hs Inhibitor Inhibition 90.2 89.0 109.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Antigen presentation
Immuno Process:  Immune regulation
Immuno Process:  Cytokine production & signalling
Immuno Process:  Cellular signalling

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. Anderson DR, Meyers MJ, Vernier WF, Mahoney MW, Kurumbail RG, Caspers N, Poda GI, Schindler JF, Reitz DB, Mourey RJ. (2007) Pyrrolopyridine inhibitors of mitogen-activated protein kinase-activated protein kinase 2 (MK-2). J Med Chem, 50 (11): 2647-54. [PMID:17480064]

3. 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]

4. Davis T, Bagley MC, Dix MC, Murziani PG, Rokicki MJ, Widdowson CS, Zayed JM, Bachler MA, Kipling D. (2007) Synthesis and in vivo activity of MK2 and MK2 substrate-selective p38alpha(MAPK) inhibitors in Werner syndrome cells. Bioorg Med Chem Lett, 17 (24): 6832-5. [PMID:17964780]

5. 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]

6. Hillig RC, Eberspaecher U, Monteclaro F, Huber M, Nguyen D, Mengel A, Muller-Tiemann B, Egner U. (2007) Structural basis for a high affinity inhibitor bound to protein kinase MK2. J Mol Biol, 369 (3): 735-45. [PMID:17449059]

7. Lovering F, Kirincich S, Wang W, Combs K, Resnick L, Sabalski JE, Butera J, Liu J, Parris K, Telliez JB. (2009) Identification and SAR of squarate inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2). Bioorg Med Chem, 17 (9): 3342-51. [PMID:19364658]

8. Malona J, Chuaqui C, Seletsky BM, Beebe L, Cantin S, Kalken DV, Fahnoe K, Wang Z, Browning B, Szabo H et al.. (2022) Discovery of CC-99677, a selective targeted covalent MAPKAPK2 (MK2) inhibitor for autoimmune disorders. Transl Res, 249: 49-73. [PMID:35691544]

9. Meng W, Swenson LL, Fitzgibbon MJ, Hayakawa K, Ter Haar E, Behrens AE, Fulghum JR, Lippke JA. (2002) Structure of mitogen-activated protein kinase-activated protein (MAPKAP) kinase 2 suggests a bifunctional switch that couples kinase activation with nuclear export. J Biol Chem, 277 (40): 37401-5. [PMID:12171911]

10. Mourey RJ, Burnette BL, Brustkern SJ, Daniels JS, Hirsch JL, Hood WF, Meyers MJ, Mnich SJ, Pierce BS, Saabye MJ et al.. (2010) A benzothiophene inhibitor of mitogen-activated protein kinase-activated protein kinase 2 inhibits tumor necrosis factor alpha production and has oral anti-inflammatory efficacy in acute and chronic models of inflammation. J Pharmacol Exp Ther, 333 (3): 797-807. [PMID:20237073]

11. Schlapbach A, Feifel R, Hawtin S, Heng R, Koch G, Moebitz H, Revesz L, Scheufler C, Velcicky J, Waelchli R et al.. (2008) Pyrrolo-pyrimidones: a novel class of MK2 inhibitors with potent cellular activity. Bioorg Med Chem Lett, 18 (23): 6142-6. [PMID:18945615]

12. 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

MAPKAPK subfamily: MAPK activated protein kinase 2. Last modified on 29/08/2022. Accessed on 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2094.