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tyrosine kinase non receptor 2

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Target id: 2246

Nomenclature: tyrosine kinase non receptor 2

Abbreviated Name: Ack

Family: Ack family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1038 3q29 TNK2 tyrosine kinase non receptor 2
Mouse - 1055 16 B3 Tnk2 tyrosine kinase, non-receptor, 2
Rat - 1040 11q22 Tnk2 tyrosine kinase, non-receptor, 2
Previous and Unofficial Names Click here for help
ACK1 | activated Cdc42-associated kinase 1 | Pyk1 | tyrosine kinase
Database Links Click here for help
Alphafold Q07912 (Hs), O54967 (Mm), Q5U2X5 (Rn)
BRENDA 2.7.10.2
CATH/Gene3D 4.10.680.10
ChEMBL Target CHEMBL4599 (Hs), CHEMBL2079848 (Mm)
Ensembl Gene ENSG00000061938 (Hs), ENSMUSG00000022791 (Mm), ENSRNOG00000001769 (Rn)
Entrez Gene 10188 (Hs), 51789 (Mm), 303882 (Rn)
Human Protein Atlas ENSG00000061938 (Hs)
KEGG Enzyme 2.7.10.2
KEGG Gene hsa:10188 (Hs), mmu:51789 (Mm), rno:303882 (Rn)
OMIM 606994 (Hs)
Pharos Q07912 (Hs)
RefSeq Nucleotide NM_001010938 (Hs), NM_016788 (Mm), NM_001008336 (Rn)
RefSeq Protein NP_001010938 (Hs), NP_058068 (Mm), NP_001008337 (Rn)
UniProtKB Q07912 (Hs), O54967 (Mm), Q5U2X5 (Rn)
Wikipedia TNK2 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of Ack1 (TNK2) with compound T74.
PDB Id:  3EQR
Resolution:  2.0Å
Species:  Human
References:  6
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of Ack1 (TNK2) kinase domain.
PDB Id:  4HZR
Resolution:  1.31Å
Species:  Human
References:  4
Enzyme Reaction Click here for help
EC Number: 2.7.10.2

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 30 [PMID: 17280833] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.0 pIC50 3
⤷ pIC50 9.0 (IC50 1x10-9 M) [3]
bosutinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.6 pIC50 7
⤷ pIC50 8.6 (IC50 2.7x10-9 M) [7]
NIK inhibitor 12f Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.7 pIC50 9
⤷ pIC50 6.7 (IC50 1.917x10-7 M) [9]
Description: Inhibitory concentration determined in a Reaction Biology kinase sreening assay.
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: TNK2
Ligand Sp. Type Action Value Parameter
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.7 pKd
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.3 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.2 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.8 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure 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
fedratinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.2 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.2 pKd
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.9 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.7 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: 1,5
Key to terms and symbols Click column headers to sort
Target used in screen: ACK1/ACK1
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 0.5 11.0 -1.0
K-252a Small molecule or natural product Hs Inhibitor Inhibition 1.0 0.0 0.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 2.2 -1.5 0.0
PP1 analog II Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 2.4 6.0 2.0
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 2.4 8.0 13.0
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 2.6
Lck inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 2.7 4.0 1.0
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 2.8 3.0 0.0
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 3.5
JAK inhibitor I Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 4.4 10.0 0.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Antigen presentation

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. DiMauro EF, Newcomb J, Nunes JJ, Bemis JE, Boucher C, Buchanan JL, Buckner WH, Cheng A, Faust T, Hsieh F et al.. (2007) Discovery of 4-amino-5,6-biaryl-furo[2,3-d]pyrimidines as inhibitors of Lck: development of an expedient and divergent synthetic route and preliminary SAR. Bioorg Med Chem Lett, 17 (8): 2305-9. [PMID:17280833]

4. Gajiwala KS, Maegley K, Ferre R, He YA, Yu X. (2013) Ack1: activation and regulation by allostery. PLoS ONE, 8 (1): e53994. [PMID:23342057]

5. 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]

6. Kopecky DJ, Hao X, Chen Y, Fu J, Jiao X, Jaen JC, Cardozo MG, Liu J, Wang Z, Walker NP et al.. (2008) Identification and optimization of N3,N6-diaryl-1H-pyrazolo[3,4-d]pyrimidine-3,6-diamines as a novel class of ACK1 inhibitors. Bioorg Med Chem Lett, 18 (24): 6352-6. [PMID:18993068]

7. Remsing Rix LL, Rix U, Colinge J, Hantschel O, Bennett KL, Stranzl T, Müller A, Baumgartner C, Valent P, Augustin M et al.. (2009) Global target profile of the kinase inhibitor bosutinib in primary chronic myeloid leukemia cells. Leukemia, 23 (3): 477-85. [PMID:19039322]

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. Zhu Y, Ma Y, Zu W, Song J, Wang H, Zhong Y, Li H, Zhang Y, Gao Q, Kong B et al.. (2020) Identification of N-Phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine Derivatives as Novel, Potent, and Selective NF-κB Inducing Kinase (NIK) Inhibitors for the Treatment of Psoriasis. J Med Chem, 63 (13): 6748-6773. [PMID:32479083]

How to cite this page

Ack family: tyrosine kinase non receptor 2. Last modified on 04/06/2020. Accessed on 11/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2246.