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MAPK interacting serine/threonine kinase 1

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Target not currently curated in GtoImmuPdb

Target id: 2104

Nomenclature: MAPK interacting serine/threonine kinase 1

Abbreviated Name: Mnk1

Family: MKN subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 465 1p33 MKNK1 MAPK interacting serine/threonine kinase 1
Mouse - 427 4 D1 Mknk1 MAP kinase-interacting serine/threonine kinase 1
Rat - 413 5q35 Mknk1 MAPK interacting serine/threonine kinase 1
Previous and Unofficial Names Click here for help
MAP kinase signal-integrating kinase 1 | MAP kinase interacting serine/threonine kinase 1 | MAP kinase-interacting serine/threonine kinase 1
Database Links Click here for help
Alphafold Q9BUB5 (Hs), O08605 (Mm), Q4G050 (Rn)
BRENDA 2.7.11.1
ChEMBL Target CHEMBL4718 (Hs), CHEMBL4523120 (Mm)
Ensembl Gene ENSG00000079277 (Hs), ENSMUSG00000028708 (Mm), ENSRNOG00000010381 (Rn)
Entrez Gene 8569 (Hs), 17346 (Mm), 500526 (Rn)
Human Protein Atlas ENSG00000079277 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:8569 (Hs), mmu:17346 (Mm), rno:500526 (Rn)
OMIM 606724 (Hs)
Pharos Q9BUB5 (Hs)
RefSeq Nucleotide NM_001135553 (Hs), NM_021461 (Mm), NM_001044267 (Rn)
RefSeq Protein NP_001129025 (Hs), NP_067436 (Mm), NP_001037732 (Rn)
UniProtKB Q9BUB5 (Hs), O08605 (Mm), Q4G050 (Rn)
Wikipedia MKNK1 (Hs)
Selected 3D Structures Click here for help
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 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
tomivosertib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.6 pIC50 7
⤷ pIC50 8.6 (IC50 2.4x10-9 M) [7]
Description: Biochemical inhibition assay.
compound 20j [PMID: 38564512] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.4 pIC50 10
⤷ pIC50 8.4 (IC50 4.4x10-9 M) [10]
dorsomorphin Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure 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
tinodasertib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.2 pIC50 9
⤷ pIC50 7.2 (IC50 6.4x10-8 M) [9]
MNK1 inhibitor Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 6.1 pIC50 6
⤷ pIC50 6.1 (IC50 8.7x10-7 M) [6]
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: 2,8
Key to terms and symbols Click column headers to sort
Target used in screen: MKNK1
Ligand Sp. Type Action Value Parameter
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 7.6 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.3 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.1 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.8 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.6 pKd
sorafenib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.6 pKd
canertinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 6.6 pKd
gefitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.5 pKd
vandetanib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.4 pKd
erlotinib Small molecule or natural product Approved drug Ligand has a PDB structure 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 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
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 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.9
K-252a Small molecule or natural product Hs Inhibitor Inhibition 12.7
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 20.3
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 23.4
JAK3 inhibitor II Small molecule or natural product Hs Inhibitor Inhibition 32.7
BPIQ-I Small molecule or natural product Hs Inhibitor Inhibition 39.9
dorsomorphin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 40.4
gefitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 41.9
compound 56 [PMID: 8568816] Small molecule or natural product Hs Inhibitor Inhibition 46.0
SB 218078 Small molecule or natural product 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]

9. Yang H, Chennamaneni LR, Ho MWT, Ang SH, Tan ESW, Jeyaraj DA, Yeap YS, Liu B, Ong EH, Joy JK et al.. (2018) Optimization of Selective Mitogen-Activated Protein Kinase Interacting Kinases 1 and 2 Inhibitors for the Treatment of Blast Crisis Leukemia. J Med Chem, 61 (10): 4348-4369. [PMID:29683667]

10. Yuan X, Guan D, Chen C, Guo S, Wu H, Bu H, Yang CY, Wang M, Zhou J, Zhang H. (2024) Development of an Imidazopyridazine-Based MNK1/2 Inhibitor for the Treatment of Lymphoma. J Med Chem, 67 (7): 5437-5457. [PMID:38564512]

How to cite this page

MKN subfamily: MAPK interacting serine/threonine kinase 1. Last modified on 04/04/2024. Accessed on 04/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2104.