IL2 inducible T-cell kinase

Target id: 2046

Nomenclature: IL2 inducible T-cell kinase

Abbreviated Name: ITK

Family: Tec family

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for IL2 inducible T-cell kinase in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 620 5q31-q32 ITK IL2 inducible T-cell kinase
Mouse - 619 11 B1.1 Itk IL2 inducible T cell kinase
Rat - 626 10 q21 Itk IL2-inducible T-cell kinase
Previous and Unofficial Names
EMT | T-cell-specific kinase | Tcsk | tyrosine-protein kinase ITK/TSK | Tyrosine-protein kinase Lyk
Database Links
BRENDA
CATH/Gene3D
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  CRYSTAL STRUCTURE OF APO INTERLEUKIN-2 TYROSINE KINASE CATALYTIC DOMAIN
PDB Id:  1SNX
Resolution:  3.2Å
Species:  Human
References:  3
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of interleukin-2 inducible T-cell kinase (ITK) catalytic domain with thienopyrazolylindole inhibitor 477.
PDB Id:  3V8T
Ligand:  compound 7 [PMID: 22464456]
Resolution:  2.0Å
Species:  Human
References:  8
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 Affinity Units Reference
WZ4002 Hs Inhibition 7.4 pKd 11
pKd 7.4 (Kd 4.3x10-8 M) [11]
compound 7 [PMID: 22464456] Hs Inhibition 9.5 pIC50 8
pIC50 9.5 (IC50 3x10-10 M) [8]
PRN694 Hs Inhibition 9.5 pIC50 10
pIC50 9.5 (IC50 3x10-10 M) [10]
ibrutinib Hs Inhibition 8.3 pIC50 4
pIC50 8.3 (IC50 4.9x10-9 M) [4]
compound 4g [PMID: 21316219] Hs Inhibition 7.2 pIC50 7
pIC50 7.2 (IC50 6x10-8 M) [7]
acalabrutinib Hs Inhibition <6.0 pIC50 4
pIC50 <6.0 (IC50 >1x10-6 M) [4]
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: 5,9

Key to terms and symbols Click column headers to sort
Target used in screen: ITK
Ligand Sp. Type Action Affinity Units
sunitinib Hs Inhibitor Inhibition 7.9 pKd
staurosporine Hs Inhibitor Inhibition 7.7 pKd
NVP-TAE684 Hs Inhibitor Inhibition 7.5 pKd
foretinib Hs Inhibitor Inhibition 7.2 pKd
SU-14813 Hs Inhibitor Inhibition 6.7 pKd
KW-2449 Hs Inhibitor Inhibition 6.6 pKd
lestaurtinib Hs Inhibitor Inhibition 6.5 pKd
tozasertib Hs Inhibitor Inhibition 6.5 pKd
tamatinib Hs Inhibitor Inhibition 6.4 pKd
fedratinib Hs Inhibitor Inhibition 6.3 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: 1,6

Key to terms and symbols Click column headers to sort
Target used in screen: Itk/ITK
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Hs Inhibitor Inhibition 2.9 2.5 0.5
Gö 6976 Hs Inhibitor Inhibition 4.3 4.0 4.0
SB 218078 Hs Inhibitor Inhibition 8.3 88.0 70.0
Syk inhibitor Hs Inhibitor Inhibition 21.4 8.0 1.0
K-252a Hs Inhibitor Inhibition 22.7 15.0 1.0
SU11652 Hs Inhibitor Inhibition 30.0 21.0 2.0
indirubin derivative E804 Hs Inhibitor Inhibition 34.8 24.0 2.0
dorsomorphin Hs Inhibitor Inhibition 39.9 54.0 9.0
GSK-3 inhibitor XIII Hs Inhibitor Inhibition 45.4 5.0 0.0
GSK-3 inhibitor IX Hs Inhibitor Inhibition 46.6 22.0 9.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
Disease:  Lymphoproliferative syndrome 1
Synonyms: Autosomal recessive lymphoproliferative disease [Orphanet: ORPHA238505]
Lymphoproliferative disease [Disease Ontology: DOID:619]
Disease Ontology: DOID:619
OMIM: 613011
Orphanet: ORPHA238505

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. Berg LJ, Finkelstein LD, Lucas JA, Schwartzberg PL. (2005) Tec family kinases in T lymphocyte development and function. Annu. Rev. Immunol.23: 549-600. [PMID:15771581]

3. Brown K, Long JM, Vial SC, Dedi N, Dunster NJ, Renwick SB, Tanner AJ, Frantz JD, Fleming MA, Cheetham GM. (2004) Crystal structures of interleukin-2 tyrosine kinase and their implications for the design of selective inhibitors. J. Biol. Chem.279 (18): 18727-32. [PMID:14766749]

4. Byrd JC, Harrington B, O'Brien S, Jones JA, Schuh A, Devereux S, Chaves J, Wierda WG, Awan FT, Brown JR et al.. (2015) Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia. N. Engl. J. Med.,  [Epub ahead of print]. [PMID:26641137]

5. 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]

6. 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]

7. Herdemann M, Weber A, Jonveaux J, Schwoebel F, Stoeck M, Heit I. (2011) Optimisation of ITK inhibitors through successive iterative design cycles. Bioorg. Med. Chem. Lett.21 (6): 1852-6. [PMID:21316219]

8. McLean LR, Zhang Y, Zaidi N, Bi X, Wang R, Dharanipragada R, Jurcak JG, Gillespy TA, Zhao Z, Musick KY et al.. (2012) X-ray crystallographic structure-based design of selective thienopyrazole inhibitors for interleukin-2-inducible tyrosine kinase. Bioorg. Med. Chem. Lett.22 (9): 3296-300. [PMID:22464456]

9. 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]

10. Zhong Y, Dong S, Strattan E, Ren L, Butchar JP, Thornton K, Mishra A, Porcu P, Bradshaw JM, Bisconte A et al.. (2015) Targeting interleukin-2-inducible T-cell kinase (ITK) and resting lymphocyte kinase (RLK) using a novel covalent inhibitor PRN694. J. Biol. Chem.290 (10): 5960-78. [PMID:25593320]

11. Zhou W, Ercan D, Chen L, Yun CH, Li D, Capelletti M, Cortot AB, Chirieac L, Iacob RE, Padera R et al.. (2009) Novel mutant-selective EGFR kinase inhibitors against EGFR T790M. Nature462 (7276): 1070-4. [PMID:20033049]

How to cite this page

Tec family: IL2 inducible T-cell kinase. Last modified on 15/08/2017. Accessed on 13/12/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2046.