MAP kinase interacting serine/threonine kinase 1 | MKN subfamily | IUPHAR/BPS Guide to PHARMACOLOGY

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MAP kinase interacting serine/threonine kinase 1

Target not currently curated in GtoImmuPdb

Target id: 2104

Nomenclature: MAP kinase interacting serine/threonine kinase 1

Abbreviated Name: Mnk1

Family: MKN subfamily

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

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 424 1p33 MKNK1 MAP kinase interacting serine/threonine kinase 1
Mouse - 415 4 D1 Mknk1 MAP kinase-interacting serine/threonine kinase 1
Rat - 413 5 q36 Mknk1 MAP kinase-interacting serine/threonine kinase 1
Previous and Unofficial Names
MAP kinase signal-integrating kinase 1
Database Links
BRENDA
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of Mnk1 catalytic domain
PDB Id:  2HW6
Resolution:  2.5Å
Species:  Human
References:  4
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human ERK2 complexed with a MAPK docking peptide
PDB Id:  2Y9Q
Resolution:  1.55Å
Species:  Human
References:  3
Enzyme Reaction
EC Number: 2.7.11.1

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 Parameter Reference
tomivosertib Hs Inhibition 8.6 pIC50 7
pIC50 8.6 (IC50 2.4x10-9 M) [7]
Description: Biochemical inhibition assay.
dorsomorphin Hs Inhibition 8.0 pIC50 5
pIC50 8.0 (IC50 1.1x10-8 M) [5]
Description: Assayed using AMPK heterotrimeric complex containing α2, β1, γ1 subunits
MNK1 inhibitor Hs Inhibition 6.1 pIC50 6
pIC50 6.1 (IC50 8.7x10-7 M) [6]
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: 2,8

Key to terms and symbols Click column headers to sort
Target used in screen: MKNK1
Ligand Sp. Type Action Affinity Parameter
AST-487 Hs Inhibitor Inhibition 7.6 pKd
lestaurtinib Hs Inhibitor Inhibition 7.3 pKd
foretinib Hs Inhibitor Inhibition 7.1 pKd
staurosporine Hs Inhibitor Inhibition 6.8 pKd
sorafenib Hs Inhibitor Inhibition 6.6 pKd
tamatinib Hs Inhibitor Inhibition 6.6 pKd
canertinib Hs Inhibitor Inhibition 6.6 pKd
gefitinib Hs Inhibitor Inhibition 6.5 pKd
vandetanib Hs Inhibitor Inhibition 6.4 pKd
erlotinib Hs Inhibitor Inhibition 6.2 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/MNK1
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
PKR inhibitor Hs Inhibitor Inhibition 9.9
K-252a Hs Inhibitor Inhibition 12.7
staurosporine Hs Inhibitor Inhibition 20.3
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 23.4
JAK3 inhibitor II Hs Inhibitor Inhibition 32.7
BPIQ-I Hs Inhibitor Inhibition 39.9
dorsomorphin Hs Inhibitor Inhibition 40.4
gefitinib Hs Inhibitor Inhibition 41.9
compound 56 [PMID: 8568816] Hs Inhibitor Inhibition 46.0
SB 218078 Hs Inhibitor Inhibition 48.6
Displaying the top 10 most potent ligands  View all ligands in screen »

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. Garai Á, Zeke A, Gógl G, Törő I, Fördős F, Blankenburg H, Bárkai T, Varga J, Alexa A, Emig D et al.. (2012) Specificity of linear motifs that bind to a common mitogen-activated protein kinase docking groove. Sci Signal, 5 (245): ra74. [PMID:23047924]

4. Jauch R, Cho MK, Jäkel S, Netter C, Schreiter K, Aicher B, Zweckstetter M, Jäckle H, Wahl MC. (2006) Mitogen-activated protein kinases interacting kinases are autoinhibited by a reprogrammed activation segment. EMBO J., 25 (17): 4020-32. [PMID:16917500]

5. Machrouhi F, Ouhamou N, Laderoute K, Calaoagan J, Bukhtiyarova M, Ehrlich PJ, Klon AE. (2010) The rational design of a novel potent analogue of the 5'-AMP-activated protein kinase inhibitor compound C with improved selectivity and cellular activity. Bioorg. Med. Chem. Lett., 20 (22): 6394-9. [PMID:20932747]

6. Oyarzabal J, Zarich N, Albarran MI, Palacios I, Urbano-Cuadrado M, Mateos G, Reymundo I, Rabal O, Salgado A, Corrionero A et al.. (2010) Discovery of mitogen-activated protein kinase-interacting kinase 1 inhibitors by a comprehensive fragment-oriented virtual screening approach. J. Med. Chem., 53 (18): 6618-28. [PMID:20722422]

7. Reich SH, Sprengeler PA, Chiang GG, Appleman JR, Chen J, Clarine J, Eam B, Ernst JT, Han Q, Goel VK et al.. (2018) Structure-based Design of Pyridone-Aminal eFT508 Targeting Dysregulated Translation by Selective Mitogen-activated Protein Kinase Interacting Kinases 1 and 2 (MNK1/2) Inhibition. J. Med. Chem., 61 (8): 3516-3540. [PMID:29526098]

8. 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

MKN subfamily: MAP kinase interacting serine/threonine kinase 1. Last modified on 10/01/2019. Accessed on 20/02/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2104.