NIMA related kinase 2 | NIMA (never in mitosis gene a)- related kinase (NEK) family | IUPHAR/BPS Guide to PHARMACOLOGY

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NIMA related kinase 2

Target not currently curated in GtoImmuPdb

Target id: 2117

Nomenclature: NIMA related kinase 2

Abbreviated Name: NEK2

Family: NIMA (never in mitosis gene a)- related kinase (NEK) family

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 - 445 1q32-q42 NEK2 NIMA related kinase 2
Mouse - 443 1 H6 Nek2 NIMA (never in mitosis gene a)-related expressed kinase 2
Rat - 443 13 q27 Nek2 NIMA-related kinase 2
Previous and Unofficial Names
HSPK 21 | NLK1 | NIMA (never in mitosis gene a)-related expressed kinase 2 | NIMA-related kinase 2
Database Links
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  HUMAN NEK2 KINASE ADP-BOUND
PDB Id:  2W5A
Resolution:  1.55Å
Species:  Human
References:  6
Image of receptor 3D structure from RCSB PDB
Description:  STRUCTURE OF NEK2 BOUND TO AMINOPYRAZINE COMPOUND 12
PDB Id:  2XKD
Resolution:  1.96Å
Species:  Human
References:  7
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 Value Parameter Reference
compound 2 [PMID: 21627121] Hs Inhibition >8.2 pIC50 5
pIC50 >8.2 (IC50 <6x10-9 M) [5]
GSK579289A Hs Inhibition 7.7 pIC50 3
pIC50 7.7 (IC50 2.1x10-8 M) [3]
compound 31 [PMID: 20936789] Hs Inhibition 6.6 pIC50 7
pIC50 6.6 (IC50 2.3x10-7 M) [7]
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: NEK2
Ligand Sp. Type Action Value Parameter
PD-173955 Hs Inhibitor Inhibition 7.0 pKd
neratinib Hs Inhibitor Inhibition 6.6 pKd
tamatinib Hs Inhibitor Inhibition 6.6 pKd
GSK-461364A Hs Inhibitor Inhibition 6.6 pKd
PHA-665752 Hs Inhibitor Inhibition 6.2 pKd
staurosporine Hs Inhibitor Inhibition 6.1 pKd
pazopanib Hs Inhibitor Inhibition 6.0 pKd
SU-14813 Hs Inhibitor Inhibition 6.0 pKd
sunitinib Hs Inhibitor Inhibition 5.8 pKd
bosutinib Hs Inhibitor Inhibition 5.8 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: 1,4

Key to terms and symbols Click column headers to sort
Target used in screen: NEK2/NEK2
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
bosutinib Hs Inhibitor Inhibition 8.6
SU11274 Hs Inhibitor Inhibition 50.8 39.0 22.0
GSK-3 inhibitor X Hs Inhibitor Inhibition 73.9 101.0 87.0
Tpl2 kinase inhibitor Hs Inhibitor Inhibition 75.2 104.0 96.0
AG 1295 Hs Inhibitor Inhibition 75.7 92.0 105.0
fascaplysin Hs Inhibitor Inhibition 77.1 90.0 87.0
SU11652 Hs Inhibitor Inhibition 77.2 67.0 18.0
PKR inhibitor Hs Inhibitor Inhibition 77.2 64.0 39.0
PDK1/Akt/Flt dual pathway inhibitor Hs Inhibitor Inhibition 77.7 84.0 85.0
staurosporine Hs Inhibitor Inhibition 79.9 63.5 29.5
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
Disease:  Retinitis pigmentosa 67; RP67
Synonyms: Retinitis pigmentosa [Orphanet: ORPHA791] [Disease Ontology: DOID:10584]
Disease Ontology: DOID:10584
OMIM: 615565
Orphanet: ORPHA791

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. Emmitte KA, Adjabeng GM, Adjebang GM, Andrews CW, Alberti JG, Bambal R, Chamberlain SD, Davis-Ward RG, Dickson HD, Hassler DF et al.. (2009) Design of potent thiophene inhibitors of polo-like kinase 1 with improved solubility and reduced protein binding. Bioorg. Med. Chem. Lett., 19 (6): 1694-7. [PMID:19237286]

4. 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]

5. Henise JC, Taunton J. (2011) Irreversible Nek2 kinase inhibitors with cellular activity. J. Med. Chem., 54 (12): 4133-46. [PMID:21627121]

6. Westwood I, Cheary DM, Baxter JE, Richards MW, van Montfort RL, Fry AM, Bayliss R. (2009) Insights into the conformational variability and regulation of human Nek2 kinase. J. Mol. Biol., 386 (2): 476-85. [PMID:19124027]

7. Whelligan DK, Solanki S, Taylor D, Thomson DW, Cheung KM, Boxall K, Mas-Droux C, Barillari C, Burns S, Grummitt CG et al.. (2010) Aminopyrazine inhibitors binding to an unusual inactive conformation of the mitotic kinase Nek2: SAR and structural characterization. J. Med. Chem., 53 (21): 7682-98. [PMID:20936789]

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

NIMA (never in mitosis gene a)- related kinase (NEK) family: NIMA related kinase 2. Last modified on 29/01/2016. Accessed on 26/01/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2117.