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MAPK activated protein kinase 5

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 2096

Nomenclature: MAPK activated protein kinase 5

Abbreviated Name: MAPKAPK5

Family: MAPKAPK subfamily

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 473 12q24.12-q24.13 MAPKAPK5 MAPK activated protein kinase 5
Mouse - 473 5 F Mapkapk5 MAP kinase-activated protein kinase 5
Rat - 473 12 q16 Mapkapk5 MAPK activated protein kinase 5
Previous and Unofficial Names Click here for help
MAPKAP kinase 5 | mitogen-activated protein kinase-activated protein kinase 5 | PRAK
Database Links Click here for help
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
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
Galapagos MAPKAPK5 inhibitor D Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 7.0 – 9.0 pIC50 3-4
pIC50 7.0 – 9.0 (IC50 1x10-7 – 1x10-9 M) [4]
Description: Binned IC50 range from patent.
pIC50 7.4 (IC50 3.7x10-8 M) [3]
compound 16 [PMID: 18945615] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.6 pIC50 7
pIC50 7.6 (IC50 2.4x10-8 M) [7]
compound 16 [PMID: 17480064] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.1 pIC50 2
pIC50 6.1 (IC50 8.1x10-7 M) [2]
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: 5,9

Key to terms and symbols Click column headers to sort
Target used in screen: MAPKAPK5
Ligand Sp. Type Action Value Parameter
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.6 pKd
lestaurtinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 6.0 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 5.9 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 5.6 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
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
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
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: 1,6

Key to terms and symbols Click column headers to sort
Target used in screen: PRAK/MAPKAPK5(PRAK)
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 46.0 21.5 -0.5
K-252a Small molecule or natural product Hs Inhibitor Inhibition 47.9 19.0 0.0
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 52.2 32.0 2.0
PDK1/Akt/Flt dual pathway inhibitor Small molecule or natural product Hs Inhibitor Inhibition 66.9 93.0 80.0
compound 52 [PMID: 9677190] Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 68.6 105.0 88.0
D4476 Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 69.6 110.0 89.0
compound 56 [PMID: 8568816] Small molecule or natural product Hs Inhibitor Inhibition 71.6 79.0 82.0
fasudil Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 72.6 105.0 84.0
casein kinase II inhibitor III Small molecule or natural product Hs Inhibitor Inhibition 72.6 83.0 28.0
Chk2 inhibitor II Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 73.5 91.0 67.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
MAPKAPK5 plays a role in important inflammatory pathways. It was investigated as a novel molecular target for rheumatoid arthritis. Galapagos developed an orally available MAPKAPK5 inhibitor, GLPG0259, which reached Phase 2 clinical trial for methotrexate-refractory RA (NCT01211249). However it quickly became evident that GLPG0259 lacked efficacy in RA patients and the study was terminated [8].

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. Andrews M. Discovery of inhibitors of MAPKAPK5, a novel target for rheumatoid arthritis. Accessed on 15/03/2018. Modified on 15/03/2018. www.rsc.org, https://www.google.co.uk/url?sa=t&rct=j&q=&esrc=s&source=web&cd=7&cad=rja&uact=8&ved=0ahUKEwiEjPvHy-7ZAhUGKewKHf2vBYAQFghJMAY&url=http%3A%2F%2Fwww.rsc.org%2Fimages%2FMartinAndrews_tcm18-195242.pdf&usg=AOvVaw38oSSfFTUgOzaYq791YK8Q

4. Andrews MJI, Edwards P, Chambers MS, Schmidt W, Clase JA, Bar G, Hirst KL, Macleod A. (2007) Triazolopyrazine compounds useful for the treatment of degenerative & inflammatory diseases. Patent number: WO2007138072A2. Assignee: Galapagos N.V.. Priority date: 31/05/2006. Publication date: 06/12/2007.

5. 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]

6. 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]

7. 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]

8. Westhovens R, Keyser FD, Rekalov D, Nasonov EL, Beetens J, Van der Aa A, Wigerinck P, Namour F, Vanhoutte F, Durez P. (2013) Oral administration of GLPG0259, an inhibitor of MAPKAPK5, a new target for the treatment of rheumatoid arthritis: a phase II, randomised, double-blind, placebo-controlled, multicentre trial. Ann Rheum Dis, 72 (5): 741-4. [PMID:23161899]

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]

How to cite this page

MAPKAPK subfamily: MAPK activated protein kinase 5. Last modified on 30/04/2019. Accessed on 10/05/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2096.