tyrosine kinase non receptor 2 | Ack family | IUPHAR/BPS Guide to PHARMACOLOGY

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tyrosine kinase non receptor 2

Target not currently curated in GtoImmuPdb

Target id: 2246

Nomenclature: tyrosine kinase non receptor 2

Abbreviated Name: Ack

Family: Ack 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 - 1086 3q29 TNK2 tyrosine kinase non receptor 2
Mouse - 1055 16 B3 Tnk2 tyrosine kinase, non-receptor, 2
Rat - 1040 11 q22 Tnk2 tyrosine kinase
Previous and Unofficial Names
ACK1 | activated Cdc42-associated kinase 1 | Pyk1 | tyrosine kinase
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
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
EC Number: 2.7.10.2

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 30 [PMID: 17280833] Hs Inhibition 9.0 pIC50 3
pIC50 9.0 (IC50 1x10-9 M) [3]
bosutinib Hs Inhibition 8.6 pIC50 7
pIC50 8.6 (IC50 2.7x10-9 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: TNK2
Ligand Sp. Type Action Value Parameter
NVP-TAE684 Hs Inhibitor Inhibition 8.7 pKd
dasatinib Hs Inhibitor Inhibition 8.3 pKd
lestaurtinib Hs Inhibitor Inhibition 8.2 pKd
staurosporine Hs Inhibitor Inhibition 7.8 pKd
PD-173955 Hs Inhibitor Inhibition 7.6 pKd
bosutinib Hs Inhibitor Inhibition 7.5 pKd
fedratinib Hs Inhibitor Inhibition 7.2 pKd
tamatinib Hs Inhibitor Inhibition 7.2 pKd
midostaurin Hs Inhibitor Inhibition 6.9 pKd
foretinib 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
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 Hs Inhibitor Inhibition 0.5 11.0 -1.0
K-252a Hs Inhibitor Inhibition 1.0 0.0 0.0
staurosporine Hs Inhibitor Inhibition 2.2 -1.5 0.0
PP1 analog II Hs Inhibitor Inhibition 2.4 6.0 2.0
SB 218078 Hs Inhibitor Inhibition 2.4 8.0 13.0
dasatinib Hs Inhibitor Inhibition 2.6
Lck inhibitor Hs Inhibitor Inhibition 2.7 4.0 1.0
Gö 6976 Hs Inhibitor Inhibition 2.8 3.0 0.0
bosutinib Hs Inhibitor Inhibition 3.5
JAK inhibitor I Hs Inhibitor Inhibition 4.4 10.0 0.0
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. 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]

How to cite this page

Ack family: tyrosine kinase non receptor 2. Last modified on 20/02/2015. Accessed on 22/07/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2246.