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BMX non-receptor tyrosine kinase

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 1942

Nomenclature: BMX non-receptor tyrosine kinase

Abbreviated Name: Etk

Family: Tec family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 675 Xp22.2 BMX BMX non-receptor tyrosine kinase
Mouse - 651 X F5 Bmx BMX non-receptor tyrosine kinase
Rat - 655 X q21 Bmx BMX non-receptor tyrosine kinase
Previous and Unofficial Names Click here for help
cytoplasmic tyrosine-protein kinase BMX | ETK | PSCTK3 | Tyro8
Database Links Click here for help
Alphafold P51813 (Hs), P97504 (Mm)
BRENDA 2.7.10.2
CATH/Gene3D 3.30.505.10, 2.30.29.30
ChEMBL Target CHEMBL3834 (Hs), CHEMBL2034793 (Mm)
Ensembl Gene ENSG00000102010 (Hs), ENSMUSG00000031377 (Mm), ENSRNOG00000003705 (Rn)
Entrez Gene 660 (Hs), 12169 (Mm), 367786 (Rn)
Human Protein Atlas ENSG00000102010 (Hs)
KEGG Enzyme 2.7.10.2
KEGG Gene hsa:660 (Hs), mmu:12169 (Mm), rno:367786 (Rn)
OMIM 300101 (Hs)
Pharos P51813 (Hs)
RefSeq Nucleotide NM_001721 (Hs), NM_009759 (Mm), NM_001109016 (Rn)
RefSeq Protein NP_001712 (Hs), NP_033889 (Mm), NP_001102486 (Rn)
UniProtKB P51813 (Hs), P97504 (Mm)
Wikipedia BMX (Hs)
Selected 3D Structures Click here for help
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:  12
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
BIIB091 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.1 pKd 8
⤷ pKd 7.1 (Kd 8.8x10-8 M) [8]
compound 38 [PMID: 24915291] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.1 pIC50 9
⤷ pIC50 9.1 (IC50 7.1x10-10 M) [9]
ibrutinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 9.1 pIC50 4,11
⤷ pIC50 9.1 (IC50 8x10-10 M) [11]
pIC50 9.1 (IC50 8x10-10 M) [4]
compound 31 [PMID: 24915291] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.7 pIC50 9
⤷ pIC50 8.7 (IC50 1.9x10-9 M) [9]
nemtabrutinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.3 pIC50 13
⤷ pIC50 8.3 (IC50 5.2x10-9 M) [13]
compound 9 [PMID: 26006010] Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.1 pIC50 3
⤷ pIC50 8.1 (IC50 7.6x10-9 M) [3]
BMX-IN-1 Small molecule or natural product Primary target of this compound Hs Inhibition 8.1 pIC50 10
⤷ pIC50 8.1 (IC50 8x10-9 M) [10]
PRN694 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.8 pIC50 16
⤷ pIC50 7.8 (IC50 1.7x10-8 M) [16]
acalabrutinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.3 pIC50 4
⤷ pIC50 7.3 (IC50 4.6x10-8 M) [4]
ZYBT1 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.0 pIC50 7
⤷ pIC50 7.0 (IC50 9.1x10-8 M) [7]
JNJ-64264681 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.8 pIC50 14
⤷ pIC50 6.8 (IC50 1.72x10-7 M) [14]
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: 5,15
Key to terms and symbols Click column headers to sort
Target used in screen: BMX
Ligand Sp. Type Action Value Parameter
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.9 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.5 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.8 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.7 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.7 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.7 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.7 pKd
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.2 pKd
JNJ-28312141 Small molecule or natural product Hs Inhibitor Inhibition 6.1 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure 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 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: Bmx/BMX(ETK)
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 2.5
EGFR/ErbB-2/ErbB-4 inhibitor Small molecule or natural product Hs Inhibitor Inhibition 2.5 18.0 19.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.2 2.5 1.5
K-252a Small molecule or natural product Hs Inhibitor Inhibition 7.9 1.0 2.0
Lck inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 10.1 -1.0 3.0
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 13.7 5.0 7.0
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 14.5
TWS119 Small molecule or natural product Hs Inhibitor Inhibition 24.3 2.0 3.0
PP1 analog II Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 25.2 8.0 1.0
SB 218078 Small molecule or natural product 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)
Immuno Process:  Cellular signalling
Immuno Process:  B cell (activation)
Immuno Process:  Immune regulation

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. 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. Hopkins BT, Bame E, Bajrami B, Black C, Bohnert T, Boiselle C, Burdette D, Burns JC, Delva L, Donaldson D et al.. (2022) Discovery and Preclinical Characterization of BIIB091, a Reversible, Selective BTK Inhibitor for the Treatment of Multiple Sclerosis. J Med Chem, 65 (2): 1206-1224. [PMID:34734694]

9. 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]

10. 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]

11. 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]

12. 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]

13. 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]

14. 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]

15. 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]

16. 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 02/11/2022. Accessed on 08/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1942.