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MAPK interacting serine/threonine kinase 2

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Target id: 2105

Nomenclature: MAPK interacting serine/threonine kinase 2

Abbreviated Name: Mnk2

Family: MKN subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 465 19p13.3 MKNK2 MAPK interacting serine/threonine kinase 2
Mouse - 459 10 C1 Mknk2 MAP kinase-interacting serine/threonine kinase 2
Rat - 459 7q11 Mknk2 MAPK interacting serine/threonine kinase 2
Previous and Unofficial Names Click here for help
MAP kinase-interacting serine/threonine kinase 2 | G protein-coupled receptor kinase 7 | MAP kinase interacting serine/threonine kinase 2 | MAP kinase signal-integrating kinase 2
Database Links Click here for help
Alphafold Q9HBH9 (Hs), Q8CDB0 (Mm), Q5U2N4 (Rn)
BRENDA 2.7.11.1
ChEMBL Target CHEMBL4204 (Hs), CHEMBL4523384 (Mm)
Ensembl Gene ENSG00000099875 (Hs), ENSMUSG00000020190 (Mm), ENSRNOG00000029028 (Rn)
Entrez Gene 2872 (Hs), 17347 (Mm), 299618 (Rn)
Human Protein Atlas ENSG00000099875 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:2872 (Hs), mmu:17347 (Mm), rno:299618 (Rn)
OMIM 605069 (Hs)
Pharos Q9HBH9 (Hs)
RefSeq Nucleotide NM_017572 (Hs), NM_021462 (Mm), NM_001011985 (Rn)
RefSeq Protein NP_060042 (Hs), NP_067437 (Mm), NP_001011985 (Rn)
SynPHARM 85807 (in complex with tomivosertib)
UniProtKB Q9HBH9 (Hs), Q8CDB0 (Mm), Q5U2N4 (Rn)
Wikipedia MKNK2 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Structure of human Mnk2 Kinase Domain
PDB Id:  2AC3
Resolution:  2.1Å
Species:  Human
References:  4
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
compound 20j [PMID: 38564512] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.4 pIC50 10
⤷ pIC50 9.4 (IC50 4x10-10 M) [10]
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 9.0 pIC50 7
⤷ pIC50 9.0 (IC50 1x10-9 M) [7]
Description: Biochemical inhibition assay.
tinodasertib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.1 pIC50 9
⤷ pIC50 7.1 (IC50 8.6x10-8 M) [9]
MELK-TI Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.1 pIC50 5
⤷ pIC50 6.1 (IC50 7.6x10-7 M) [5]
Description: Measured in a MIllipore kinase screening assay
MNK1 inhibitor Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.8 pIC50 6
⤷ pIC50 5.8 (IC50 1.6x10-6 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: MKNK2
Ligand Sp. Type Action Value Parameter
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.9 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 8.5 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.4 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.8 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.4 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.9 pKd
sorafenib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.9 pKd
ruxolitinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.7 pKd
linifanib Small molecule or natural product Hs Inhibitor Inhibition 6.6 pKd
fedratinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.4 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: 1,3
Key to terms and symbols Click column headers to sort
Target used in screen: Mnk2/MNK2
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 4.2 0.0 0.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.0 9.5 4.0
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 9.7 97.0 95.0
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 17.2 6.0 14.0
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 17.6 9.0 4.0
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 18.0 10.0 10.0
JAK3 inhibitor II Small molecule or natural product Hs Inhibitor Inhibition 18.0 10.0 6.0
Flt-3 inhibitor III Small molecule or natural product Hs Inhibitor Inhibition 18.6 21.0 7.0
BPIQ-I Small molecule or natural product Hs Inhibitor Inhibition 32.2 26.0 13.0
PD 158780 Small molecule or natural product Hs Inhibitor Inhibition 32.3 21.0 12.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Immune system development

References

Show »

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. 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]

4. Jauch R, Jäkel S, Netter C, Schreiter K, Aicher B, Jäckle H, Wahl MC. (2005) Crystal structures of the Mnk2 kinase domain reveal an inhibitory conformation and a zinc binding site. Structure, 13 (10): 1559-68. [PMID:16216586]

5. Johnson CN, Berdini V, Beke L, Bonnet P, Brehmer D, Coyle JE, Day PJ, Frederickson M, Freyne EJ, Gilissen RA et al.. (2014) Fragment-based discovery of type I inhibitors of maternal embryonic leucine zipper kinase. ACS Med Chem Lett, 6 (1): 25-30. [PMID:25589925]

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 2. Last modified on 04/04/2024. Accessed on 13/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2105.