BMX non-receptor tyrosine kinase | Tec family | IUPHAR/BPS Guide to PHARMACOLOGY

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BMX non-receptor tyrosine kinase

target has curated data in GtoImmuPdb

Target id: 1942

Nomenclature: BMX non-receptor tyrosine kinase

Abbreviated Name: Etk

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 - 675 Xp22.2 BMX BMX non-receptor tyrosine kinase
Mouse - 655 X Bmx BMX non-receptor tyrosine kinase
Rat - 655 X q21 Bmx BMX non-receptor tyrosine kinase
Previous and Unofficial Names
cytoplasmic tyrosine-protein kinase BMX | ETK | PSCTK3 | Tyro8
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 BMX non-receptor tyrosine kinase complex with dasatinib
PDB Id:  3SXR
Ligand:  dasatinib
Resolution:  2.4Å
Species:  Human
References:  10
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 38 [PMID: 24915291] Hs Inhibition 9.1 pIC50 7
pIC50 9.1 (IC50 7.1x10-10 M) [7]
ibrutinib Hs Inhibition 9.1 pIC50 4,9
pIC50 9.1 (IC50 8x10-10 M) [9]
pIC50 9.1 (IC50 8x10-10 M) [4]
compound 31 [PMID: 24915291] Hs Inhibition 8.7 pIC50 7
pIC50 8.7 (IC50 1.9x10-9 M) [7]
compound 9 [PMID: 26006010] Hs Inhibition 8.1 pIC50 3
pIC50 8.1 (IC50 7.6x10-9 M) [3]
BMX-IN-1 Hs Inhibition 8.1 pIC50 8
pIC50 8.1 (IC50 8x10-9 M) [8]
PRN694 Hs Inhibition 7.8 pIC50 12
pIC50 7.8 (IC50 1.7x10-8 M) [12]
acalabrutinib Hs Inhibition 7.3 pIC50 4
pIC50 7.3 (IC50 4.6x10-8 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: 5,11

Key to terms and symbols Click column headers to sort
Target used in screen: BMX
Ligand Sp. Type Action Value Parameter
dasatinib Hs Inhibitor Inhibition 8.9 pKd
PD-173955 Hs Inhibitor Inhibition 7.5 pKd
staurosporine Hs Inhibitor Inhibition 6.8 pKd
tamatinib Hs Inhibitor Inhibition 6.7 pKd
foretinib Hs Inhibitor Inhibition 6.7 pKd
bosutinib Hs Inhibitor Inhibition 6.7 pKd
lestaurtinib Hs Inhibitor Inhibition 6.7 pKd
PP-242 Hs Inhibitor Inhibition 6.2 pKd
JNJ-28312141 Hs Inhibitor Inhibition 6.1 pKd
NVP-TAE684 Hs Inhibitor Inhibition 6.0 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: Bmx/BMX(ETK)
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
EGFR/ErbB-2/ErbB-4 inhibitor Hs Inhibitor Inhibition 2.5 18.0 19.0
dasatinib Hs Inhibitor Inhibition 2.5
staurosporine Hs Inhibitor Inhibition 6.2 2.5 1.5
K-252a Hs Inhibitor Inhibition 7.9 1.0 2.0
Lck inhibitor Hs Inhibitor Inhibition 10.1 -1.0 3.0
Gö 6976 Hs Inhibitor Inhibition 13.7 5.0 7.0
bosutinib Hs Inhibitor Inhibition 14.5
TWS119 Hs Inhibitor Inhibition 24.3 2.0 3.0
PP1 analog II Hs Inhibitor Inhibition 25.2 8.0 1.0
SB 218078 Hs Inhibitor Inhibition 27.5 14.0 33.0
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:  T cell (activation)
GO Annotations:  Associated to 1 GO processes
GO:0002250 adaptive immune response IBA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes
GO:0050853 B cell receptor signaling pathway IBA
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 1 GO processes
GO:0002250 adaptive immune response IBA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 1 GO processes
GO:0050853 B cell receptor signaling pathway IBA

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. 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. 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]

8. Liu F, Zhang X, Weisberg E, Chen S, Hur W, Wu H, Zhao Z, Wang W, Mao M, Cai C et al.. (2013) Discovery of a selective irreversible BMX inhibitor for prostate cancer. ACS Chem. Biol., 8 (7): 1423-8. [PMID:23594111]

9. Lou Y, Owens TD, Kuglstatter A, Kondru RK, Goldstein DM. (2012) Bruton's tyrosine kinase inhibitors: approaches to potent and selective inhibition, preclinical and clinical evaluation for inflammatory diseases and B cell malignancies. J. Med. Chem., 55 (10): 4539-50. [PMID:22394077]

10. Muckelbauer J, Sack JS, Ahmed N, Burke J, Chang CY, Gao M, Tino J, Xie D, Tebben AJ. (2011) X-ray crystal structure of bone marrow kinase in the x chromosome: a Tec family kinase. Chem Biol Drug Des, 78 (5): 739-48. [PMID:21883956]

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: BMX non-receptor tyrosine kinase. Last modified on 16/07/2019. Accessed on 08/12/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1942.