TXK tyrosine kinase | Tec family | IUPHAR/BPS Guide to PHARMACOLOGY

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TXK tyrosine kinase

target has curated data in GtoImmuPdb

Target id: 2268

Nomenclature: TXK tyrosine kinase

Abbreviated Name: TXK

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

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 527 4p12 TXK TXK tyrosine kinase
Mouse - 527 5 C3.2 Txk TXK tyrosine kinase
Rat - 526 14 p11 Txk TXK tyrosine kinase
Previous and Unofficial Names
BTKL | PSCTK5 | PTK4 protein tyrosine kinase 4 | RLK | TKL
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:  Solution structure of the SH2 domain of human tyrosine-protein kinase TXK.
PDB Id:  2DM0
Resolution:  0.0Å
Species:  Human
References: 
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
bosutinib Hs Inhibition 9.5 pIC50 10
pIC50 9.5 (IC50 3x10-10 M) [10]
compound 23 [PMID: 17600705] Hs Inhibition 9.4 pIC50 2
pIC50 9.4 (IC50 4x10-10 M) [2]
compound 38 [PMID: 24915291] Hs Inhibition 8.9 pIC50 8
pIC50 8.9 (IC50 1.4x10-9 M) [8]
PRN694 Hs Inhibition 8.9 pIC50 12
pIC50 8.9 (IC50 1.4x10-9 M) [12]
compound 31 [PMID: 24915291] Hs Inhibition 8.7 pIC50 8
pIC50 8.7 (IC50 1.9x10-9 M) [8]
ibrutinib Hs Inhibition 8.7 pIC50 5
pIC50 8.7 (IC50 2x10-9 M) [5]
compound 9 [PMID: 26006010] Hs Inhibition 7.4 pIC50 4
pIC50 7.4 (IC50 4.1x10-8 M) [4]
compound 7 [PMID: 22464456] Hs Inhibition 7.1 pIC50 9
pIC50 7.1 (IC50 7.75x10-8 M) [9]
acalabrutinib Hs Inhibition 6.4 pIC50 5
pIC50 6.4 (IC50 3.68x10-7 M) [5]
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: 6,11

Key to terms and symbols Click column headers to sort
Target used in screen: TXK
Ligand Sp. Type Action Value Parameter
dasatinib Hs Inhibitor Inhibition 8.7 pKd
PD-173955 Hs Inhibitor Inhibition 7.5 pKd
bosutinib Hs Inhibitor Inhibition 7.1 pKd
tamatinib Hs Inhibitor Inhibition 6.8 pKd
staurosporine Hs Inhibitor Inhibition 6.6 pKd
PP-242 Hs Inhibitor Inhibition 6.5 pKd
NVP-TAE684 Hs Inhibitor Inhibition 6.3 pKd
foretinib Hs Inhibitor Inhibition 6.3 pKd
KW-2449 Hs Inhibitor Inhibition 6.2 pKd
lestaurtinib Hs Inhibitor Inhibition 6.2 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: 1,7

Key to terms and symbols Click column headers to sort
Target used in screen: Txk/TXK
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
dasatinib Hs Inhibitor Inhibition 1.4
EGFR/ErbB-2/ErbB-4 inhibitor Hs Inhibitor Inhibition 1.7 52.0 14.0
Gö 6976 Hs Inhibitor Inhibition 6.4 8.0 8.0
staurosporine Hs Inhibitor Inhibition 7.3 22.5 4.0
Lck inhibitor Hs Inhibitor Inhibition 17.3 18.0 1.0
SB 218078 Hs Inhibitor Inhibition 22.7 71.0 81.0
K-252a Hs Inhibitor Inhibition 24.4 35.0 5.0
TWS119 Hs Inhibitor Inhibition 24.5 27.0 3.0
indirubin derivative E804 Hs Inhibitor Inhibition 25.6 31.0 3.0
bosutinib Hs Inhibitor Inhibition 27.5
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
The TEC family protein tyrosine kinases have been identified as key components of T-cell-receptor activation and signalling. TEC family kinases are expressed predominantly by haematopoietic cells. T cells express ITK, TXK and TEC [3].
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes
GO:0060335 positive regulation of interferon-gamma-mediated signaling pathway IDA
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 1 GO processes
GO:0002250 adaptive immune response ISS
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 1 GO processes
GO:0002250 adaptive immune response ISS
Immuno Process:  Immune regulation
GO Annotations:  Associated to 2 GO processes
GO:0050852 T cell receptor signaling pathway ISS
GO:0060335 positive regulation of interferon-gamma-mediated signaling pathway IDA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 3 GO processes
GO:0001816 cytokine production ISS
GO:0032729 positive regulation of interferon-gamma production IDA
GO:0060335 positive regulation of interferon-gamma-mediated signaling pathway IDA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes
GO:0050852 T cell receptor signaling pathway ISS

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. Bamborough P, Angell RM, Bhamra I, Brown D, Bull J, Christopher JA, Cooper AW, Fazal LH, Giordano I, Hind L et al.. (2007) N-4-Pyrimidinyl-1H-indazol-4-amine inhibitors of Lck: indazoles as phenol isosteres with improved pharmacokinetics. Bioorg. Med. Chem. Lett., 17 (15): 4363-8. [PMID:17600705]

3. 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]

4. Bradshaw JM, McFarland JM, Paavilainen VO, Bisconte A, Tam D, Phan VT, Romanov S, Finkle D, Shu J, Patel V et al.. (2015) Prolonged and tunable residence time using reversible covalent kinase inhibitors. Nat. Chem. Biol., 11 (7): 525-31. [PMID:26006010]

5. Byrd JC, Harrington B, O'Brien S, Jones JA, Schuh A, Devereux S, Chaves J, Wierda WG, Awan FT, Brown JR et al.. (2016) Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia. N. Engl. J. Med., 374 (4): 323-32. [PMID:26641137]

6. 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]

7. 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]

8. Li X, Zuo Y, Tang G, Wang Y, Zhou Y, Wang X, Guo T, Xia M, Ding N, Pan Z. (2014) Discovery of a series of 2,5-diaminopyrimidine covalent irreversible inhibitors of Bruton's tyrosine kinase with in vivo antitumor activity. J. Med. Chem., 57 (12): 5112-28. [PMID:24915291]

9. 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]

10. 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]

11. 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]

12. 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]

How to cite this page

Tec family: TXK tyrosine kinase. Last modified on 16/01/2018. Accessed on 18/09/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2268.