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TRAF2 and NCK interacting kinase

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Target id: 2244

Nomenclature: TRAF2 and NCK interacting kinase

Abbreviated Name: TNIK

Family: MSN subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1360 3q26.2-q26.31 TNIK TRAF2 and NCK interacting kinase
Mouse - 1323 3 A3 Tnik TRAF2 and NCK interacting kinase
Rat - 1354 2 q24 Tnik TRAF2 and NCK interacting kinase
Database Links Click here for help
Alphafold Q9UKE5 (Hs), P83510 (Mm)
BRENDA 2.7.11.1
ChEMBL Target CHEMBL4527 (Hs)
Ensembl Gene ENSG00000154310 (Hs), ENSMUSG00000027692 (Mm), ENSRNOG00000012422 (Rn)
Entrez Gene 23043 (Hs), 665113 (Mm), 294917 (Rn)
Human Protein Atlas ENSG00000154310 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:23043 (Hs), mmu:665113 (Mm), rno:294917 (Rn)
OMIM 610005 (Hs)
Pharos Q9UKE5 (Hs)
RefSeq Nucleotide NM_001161560 (Hs), NM_001163007 (Mm), NM_001106422 (Rn)
RefSeq Protein NP_001155032 (Hs), NP_001156479 (Mm), NP_001099892 (Rn)
UniProtKB Q9UKE5 (Hs), P83510 (Mm)
Wikipedia TNIK (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the kinase domain of human Traf2- and Nck-Interacting kinase with Wee1Chk1 Inhibitor.
PDB Id:  2X7F
Resolution:  2.8Å
Species:  Human
References: 
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
INS018_055 Small molecule or natural product Hs Inhibition 8.4 pKd 5
⤷ pKd 8.4 (Kd 4.32x10-9 M) [5]
Description: Binding affinity determined by surface plasmon resonance assay.
staurosporine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.9 pIC50 3
⤷ pIC50 8.9 (IC50 1.4x10-9 M) [3]
compound 5 [PMID: 23232060] Small molecule or natural product Hs Inhibition 8.5 pIC50 3
⤷ pIC50 8.5 (IC50 3x10-9 M) [3]
PF06260933 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.8 pIC50 1
⤷ pIC50 7.8 (IC50 1.5x10-8 M) [1]
compound 21k [PMID: 34985886] Small molecule or natural product Hs Inhibition 7.6 pIC50 4
⤷ pIC50 7.6 (IC50 2.6x10-8 M) [4]
INS018_055 Small molecule or natural product Hs Inhibition 7.5 pIC50 5
⤷ pIC50 7.5 (IC50 3.1x10-8 M) [5]
compound 25c [PMID: 36649216] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.4 pIC50 6
⤷ pIC50 6.4 (IC50 3.67x10-7 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: 2,7
Key to terms and symbols Click column headers to sort
Target used in screen: TNIK
Ligand Sp. Type Action Value Parameter
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.3 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.3 pKd
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 7.6 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.6 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 7.6 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.5 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 7.2 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 7.1 pKd
doramapimod Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.8 pKd
neratinib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 6.8 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »

References

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1. Ammirati M, Bagley SW, Bhattacharya SK, Buckbinder L, Carlo AA, Conrad R, Cortes C, Dow RL, Dowling MS, El-Kattan A et al.. (2015) Discovery of an in Vivo Tool to Establish Proof-of-Concept for MAP4K4-Based Antidiabetic Treatment. ACS Med Chem Lett, 6 (11): 1128-33. [PMID:26617966]

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. Ho KK, Parnell KM, Yuan Y, Xu Y, Kultgen SG, Hamblin S, Hendrickson TF, Luo B, Foulks JM, McCullar MV et al.. (2013) Discovery of 4-phenyl-2-phenylaminopyridine based TNIK inhibitors. Bioorg Med Chem Lett, 23 (2): 569-73. [PMID:23232060]

4. Li Y, Zhang L, Yang R, Qiao Z, Wu M, Huang C, Tian C, Luo X, Yang W, Zhang Y et al.. (2022) Discovery of 3,4-Dihydrobenzo[f][1,4]oxazepin-5(2H)-one Derivatives as a New Class of Selective TNIK Inhibitors and Evaluation of Their Anti-Colorectal Cancer Effects. J Med Chem, 65 (3): 1786-1807. [PMID:34985886]

5. Ren F, Aliper A, Chen J, Zhao H, Rao S, Kuppe C, Ozerov IV, Zhang M, Witte K, Kruse C et al.. (2024) A small-molecule TNIK inhibitor targets fibrosis in preclinical and clinical models. Nat Biotechnol, [Epub ahead of print]. [PMID:38459338]

6. Shuai W, Bu F, Zhu Y, Wu Y, Xiao H, Pan X, Zhang J, Sun Q, Wang G, Ouyang L. (2023) Discovery of Novel Indazole Chemotypes as Isoform-Selective JNK3 Inhibitors for the Treatment of Parkinson's Disease. J Med Chem, 66 (2): 1273-1300. [PMID:36649216]

7. 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

MSN subfamily: TRAF2 and NCK interacting kinase. Last modified on 25/03/2024. Accessed on 19/09/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2244.