Top ▲

tec protein tyrosine kinase

Click here for help

Target id: 2238

Nomenclature: tec protein tyrosine kinase

Abbreviated Name: TEC

Family: Tec family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 631 4p12-p11 TEC tec protein tyrosine kinase
Mouse - 630 5 38.44 cM Tec tec protein tyrosine kinase
Rat - 629 14 p11 Tec tec protein tyrosine kinase
Previous and Unofficial Names Click here for help
PSCTK4
Database Links Click here for help
Alphafold P42680 (Hs), P24604 (Mm)
BRENDA 2.7.10.2
CATH/Gene3D 2.30.29.30, 3.30.505.10
ChEMBL Target CHEMBL4246 (Hs)
Ensembl Gene ENSG00000135605 (Hs), ENSMUSG00000029217 (Mm), ENSRNOG00000002278 (Rn)
Entrez Gene 7006 (Hs), 21682 (Mm), 84492 (Rn)
Human Protein Atlas ENSG00000135605 (Hs)
KEGG Enzyme 2.7.10.2
KEGG Gene hsa:7006 (Hs), mmu:21682 (Mm), rno:84492 (Rn)
OMIM 600583 (Hs)
Pharos P42680 (Hs)
RefSeq Nucleotide NM_003215 (Hs), NM_001113460 (Mm), NM_053432 (Rn)
RefSeq Protein NP_003206 (Hs), NP_001106931 (Mm), NP_445884 (Rn)
UniProtKB P42680 (Hs), P24604 (Mm)
Wikipedia TEC (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Solution NMR structure of PH domain of tyrosine-protein kinase Tec from Homo sapiens, Northeast Structural Genomics Consortium (NESG) target HR3504C.
PDB Id:  2LUL
Resolution:  0.0Å
Species:  Human
References: 
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
PRN694 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.5 pIC50 13
⤷ pIC50 8.5 (IC50 3.3x10-9 M) [13]
compound 9 [PMID: 26006010] Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.5 pIC50 3
⤷ pIC50 8.5 (IC50 3.4x10-9 M) [3]
nemtabrutinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.2 pIC50 9
⤷ pIC50 8.2 (IC50 5.8x10-9 M) [9]
compound 38 [PMID: 24915291] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.2 pIC50 8
⤷ pIC50 8.2 (IC50 6.3x10-9 M) [8]
ibrutinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.1 pIC50 4
⤷ pIC50 8.1 (IC50 7x10-9 M) [4]
compound 31 [PMID: 24915291] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.1 pIC50 8
⤷ pIC50 8.1 (IC50 8.2x10-9 M) [8]
ZYBT1 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.6 pIC50 7
⤷ pIC50 7.6 (IC50 2.5x10-8 M) [7]
acalabrutinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.0 pIC50 4
⤷ pIC50 7.0 (IC50 9.3x10-8 M) [4]
compound 25 [PMID: 31260299] Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.6 pIC50 12
⤷ pIC50 6.6 (IC50 2.27x10-7 M) [12]
JNJ-64264681 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.5 pIC50 10
⤷ pIC50 6.5 (IC50 3.03x10-7 M) [10]
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: 5,11
Key to terms and symbols Click column headers to sort
Target used in screen: TEC
Ligand Sp. Type Action Value Parameter
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.9 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.7 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.5 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.2 pKd
MLN-8054 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.1 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 5.9 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.9 pKd
canertinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 5.8 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 5.8 pKd
JNJ-28312141 Small molecule or natural product Hs Inhibitor Inhibition 5.7 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: 1,6
Key to terms and symbols Click column headers to sort
Target used in screen: Tec (activated)/nd
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
K-252a Small molecule or natural product Hs Inhibitor Inhibition 3.0 2.0
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 4.0 9.0
Lck inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 10.0 0.0
GSK-3 inhibitor IX Small molecule or natural product Hs Inhibitor Inhibition 15.0 13.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 17.0 2.5
TWS119 Small molecule or natural product Hs Inhibitor Inhibition 17.0 0.0
Cdk2 inhibitor IV Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 24.0 2.0
GSK-3 inhibitor XIII Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 38.0 4.0
aloisine A Small molecule or natural product Hs Inhibitor Inhibition 38.0 9.0
CGP74514A Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 39.0 7.0
Target used in screen: nd/TEC
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
PDK1/Akt/Flt dual pathway inhibitor Small molecule or natural product Hs Inhibitor Inhibition 2.4
Lck inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.3
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 11.3
Src kinase inhibitor I Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 43.3
EGFR/ErbB-2/ErbB-4 inhibitor Small molecule or natural product Hs Inhibitor Inhibition 52.1
Cdk2 inhibitor IV Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 63.0
masitinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 83.2
K-252a Small molecule or natural product Hs Inhibitor Inhibition 84.2
MK2a inhibitor Small molecule or natural product Hs Inhibitor Inhibition 86.0
MNK1 inhibitor Small molecule or natural product Hs Inhibitor Inhibition 86.0
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 [2].
Immuno Process Associations
Immuno Process:  Immune regulation
Immuno Process:  Tissue repair
Immuno Process:  Cytokine production & signalling
Immuno Process:  Cellular signalling
Immuno Process:  T cell (activation)
Immuno Process:  B cell (activation)

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. 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. 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]

4. 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]

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. Ghoshdastidar K, Patel H, Bhayani H, Patel A, Thakkar K, Patel D, Sharma M, Singh J, Mohapatra J, Chatterjee A et al.. (2020) ZYBT1, a potent, irreversible Bruton's Tyrosine Kinase (BTK) inhibitor that inhibits the C481S BTK with profound efficacy against arthritis and cancer. Pharmacol Res Perspect, 8 (4): e00565. [PMID:32790160]

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. Reiff SD, Mantel R, Smith LL, Greene JT, Muhowski EM, Fabian CA, Goettl VM, Tran M, Harrington BK, Rogers KA et al.. (2018) The BTK Inhibitor ARQ 531 Targets Ibrutinib-Resistant CLL and Richter Transformation. Cancer Discov, 8 (10): 1300-1315. [PMID:30093506]

10. Tichenor MS, Wiener JJM, Rao NL, Bacani GM, Wei J, Pooley Deckhut C, Barbay JK, Kreutter KD, Chang L, Clancy KW et al.. (2022) Discovery of JNJ-64264681: A Potent and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase. J Med Chem, 65 (21): 14326-14336. [PMID:36314537]

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. Yao X, Sun X, Jin S, Yang L, Xu H, Rao Y. (2019) Discovery of 4-Aminoquinoline-3-carboxamide Derivatives as Potent Reversible Bruton's Tyrosine Kinase Inhibitors for the Treatment of Rheumatoid Arthritis. J Med Chem, 62 (14): 6561-6574. [PMID:31260299]

13. 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: tec protein tyrosine kinase. Last modified on 02/11/2022. Accessed on 20/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2238.