LYN proto-oncogene, Src family tyrosine kinase | Src family | IUPHAR Guide to IMMUNOPHARMACOLOGY

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LYN proto-oncogene, Src family tyrosine kinase

Target id: 2060

Nomenclature: LYN proto-oncogene, Src family tyrosine kinase

Abbreviated Name: Lyn

Family: Src 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: ON :     LYN proto-oncogene, Src family tyrosine kinase has curated data in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 512 8q13 LYN LYN proto-oncogene, Src family tyrosine kinase
Mouse - 512 4 A1 Lyn LYN proto-oncogene, Src family tyrosine kinase
Rat - 512 5 q12 Lyn LYN proto-oncogene, Src family tyrosine kinase
Gene and Protein Information Comments
A shorter 491 amino acid isoform has been identified in human, mouse and rat. This shorter isoform is termed isoform B, and in all species is 21 amino acids shorter than the cononical isoform (known as isoform A).
Previous and Unofficial Names
Hck-2 | JTK8 | p53Lyn | p56Lyn | v-yes-1 Yamaguchi sarcoma viral related oncogene homolog | LYN proto-oncogene
Database Links
BRENDA
CATH/Gene3D
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:  Lyn kinase domain.
PDB Id:  3A4O
Resolution:  3.0Å
Species:  Human
References:  16
Image of receptor 3D structure from RCSB PDB
Description:  SH3 domain of the human Lyn tyrosine kinase.
PDB Id:  1W1F
Resolution:  0.0Å
Species:  Human
References:  5
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
acalabrutinib Hs Inhibition 6.0 pEC50 4
pEC50 6.0 (EC50 1x10-6 M) [4]
eCF506 Hs Inhibition 9.1 pIC50 9
pIC50 9.1 (IC50 8x10-10 M) [9]
compound 23 [PMID: 17600705] Hs Inhibition 9.0 pIC50 3
pIC50 9.0 (IC50 1x10-9 M) [3]
bosutinib Hs Inhibition 8.1 pIC50 17
pIC50 8.1 (IC50 8x10-9 M) [17]
bafetinib Hs Inhibition 8.0 pIC50 13
pIC50 8.0 (IC50 1.1x10-8 M) [13]
NG-25 Hs Inhibition 7.9 pIC50 20
pIC50 7.9 (IC50 1.29x10-8 M) [20]
ibrutinib Hs Inhibition 7.7 pIC50 6
pIC50 7.7 (IC50 2x10-8 M) [6]
pexmetinib Hs Inhibition 7.6 pIC50 2
pIC50 7.6 (IC50 2.5x10-8 M) [2]
SU6656 Hs Inhibition 6.9 pIC50 8
pIC50 6.9 (IC50 1.3x10-7 M) [8]
theliatinib Hs Inhibition 6.3 pIC50 18
pIC50 6.3 (IC50 5.01x10-7 M) [18]
compound 36 [PMID: 21958547] Hs Inhibition 6.2 pIC50 14
pIC50 6.2 (IC50 6.24x10-7 M) [14]
acalabrutinib Hs Inhibition <6.0 pIC50 6
pIC50 <6.0 (IC50 >1x10-6 M) [6]
Inhibitor Comments
Note that bosutinib has inhibitory activity at other kinases including HCK, ABL1 and SRC.
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
tolimidone Hs Activation 7.2 pEC50 19
pEC50 7.2 (EC50 6.3x10-8 M) [19]
Description: Measuring induced increased the V(max) of Lyn.
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: 7,22

Key to terms and symbols Click column headers to sort
Target used in screen: LYN
Ligand Sp. Type Action Affinity Units
dasatinib Hs Inhibitor Inhibition 9.2 pKd
PD-173955 Hs Inhibitor Inhibition 8.7 pKd
bosutinib Hs Inhibitor Inhibition 8.4 pKd
foretinib Hs Inhibitor Inhibition 8.0 pKd
AST-487 Hs Inhibitor Inhibition 7.8 pKd
tamatinib Hs Inhibitor Inhibition 7.6 pKd
staurosporine Hs Inhibitor Inhibition 7.4 pKd
masitinib Hs Inhibitor Inhibition 7.2 pKd
nilotinib Hs Inhibitor Inhibition 7.0 pKd
vandetanib Hs Inhibitor Inhibition 7.0 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: 1,12

Key to terms and symbols Click column headers to sort
Target used in screen: Lyn/LYN
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
dasatinib Hs Inhibitor Inhibition 0.4
staurosporine Hs Inhibitor Inhibition 1.2 0.5 0.0
bosutinib Hs Inhibitor Inhibition 2.1
Lck inhibitor Hs Inhibitor Inhibition 3.5 0.0 1.0
GSK-3 inhibitor IX Hs Inhibitor Inhibition 6.0 4.0 1.0
SU11652 Hs Inhibitor Inhibition 6.3 2.0 3.0
dovitinib Hs Inhibitor Inhibition 9.2
vandetanib Hs Inhibitor Inhibition 10.8
TWS119 Hs Inhibitor Inhibition 11.1 2.0 -1.0
dorsomorphin Hs Inhibitor Inhibition 12.9 14.0 2.0
Target used in screen: nd/LYN B
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
dasatinib Hs Inhibitor Inhibition 1.6
Lck inhibitor Hs Inhibitor Inhibition 5.1
staurosporine Hs Inhibitor Inhibition 5.7
bosutinib Hs Inhibitor Inhibition 6.0
dovitinib Hs Inhibitor Inhibition 12.7
GSK-3 inhibitor IX Hs Inhibitor Inhibition 14.7
vandetanib Hs Inhibitor Inhibition 16.7
masitinib Hs Inhibitor Inhibition 18.7
TWS119 Hs Inhibitor Inhibition 21.4
SU11652 Hs Inhibitor Inhibition 21.9
Displaying the top 10 most potent ligands  View all ligands in screen »

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. Bachegowda L, Morrone K, Winski SL, Mantzaris I, Bartenstein M, Ramachandra N, Giricz O, Sukrithan V, Nwankwo G, Shahnaz S et al.. (2016) Pexmetinib: A Novel Dual Inhibitor of Tie2 and p38 MAPK with Efficacy in Preclinical Models of Myelodysplastic Syndromes and Acute Myeloid Leukemia. Cancer Res., 76 (16): 4841-4849. [PMID:27287719]

3. 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]

4. Barf TA, Jans CGJM, Man PADeA, Oubrie AA, Raaijmakers HCA, Rewinkel JBM, Sterrenburg J-G, Wijkmans JCHM. (2014) 4-imidazopyridazin-1-yl-benzamides and 4-imidazotriazin-1-yl-benzamides as btk inhibitors. Patent number: US20140155385 A1. Assignee: Barf TA, Jans CGJM, Man PADeA, Oubrie AA, Raaijmakers HCA, Rewinkel JBM, Sterrenburg J-G, Wijkmans JCHM. Priority date: 19/07/2011. Publication date: 05/06/2014.

5. Bauer F, Schweimer K, Meiselbach H, Hoffmann S, Rösch P, Sticht H. (2005) Structural characterization of Lyn-SH3 domain in complex with a herpesviral protein reveals an extended recognition motif that enhances binding affinity. Protein Sci., 14 (10): 2487-98. [PMID:16155203]

6. 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]

7. 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]

8. Fedorov O, Marsden B, Pogacic V, Rellos P, Müller S, Bullock AN, Schwaller J, Sundström M, Knapp S. (2007) A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc. Natl. Acad. Sci. U.S.A., 104 (51): 20523-8. [PMID:18077363]

9. Fraser C, Dawson JC, Dowling R, Houston DR, Weiss JT, Munro AF, Muir M, Harrington L, Webster SP, Frame MC et al.. (2016) Rapid Discovery and Structure-Activity Relationships of Pyrazolopyrimidines That Potently Suppress Breast Cancer Cell Growth via SRC Kinase Inhibition with Exceptional Selectivity over ABL Kinase. J. Med. Chem., 59 (10): 4697-710. [PMID:27115835]

10. Freedman TS, Tan YX, Skrzypczynska KM, Manz BN, Sjaastad FV, Goodridge HS, Lowell CA, Weiss A. (2015) LynA regulates an inflammation-sensitive signaling checkpoint in macrophages. Elife, 4. [PMID:26517880]

11. Gao R, Ma Z, Ma M, Yu J, Chen J, Li Z, Shetty S, Fu J. (2015) Deletion of Src family kinase Lyn aggravates endotoxin-induced lung inflammation. Am. J. Physiol. Lung Cell Mol. Physiol., 309 (11): L1376-81. [PMID:26453518]

12. 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]

13. Horio T, Hamasaki T, Inoue T, Wakayama T, Itou S, Naito H, Asaki T, Hayase H, Niwa T. (2007) Structural factors contributing to the Abl/Lyn dual inhibitory activity of 3-substituted benzamide derivatives. Bioorg. Med. Chem. Lett., 17 (10): 2712-7. [PMID:17376680]

14. Kim KH, Maderna A, Schnute ME, Hegen M, Mohan S, Miyashiro J, Lin L, Li E, Keegan S, Lussier J et al.. (2011) Imidazo[1,5-a]quinoxalines as irreversible BTK inhibitors for the treatment of rheumatoid arthritis. Bioorg. Med. Chem. Lett., 21 (21): 6258-63. [PMID:21958547]

15. Lowell CA. (2004) Src-family kinases: rheostats of immune cell signaling. Mol. Immunol., 41 (6-7): 631-43. [PMID:15220000]

16. Miyano N, Kinoshita T, Nakai R, Kirii Y, Yokota K, Tada T. (2009) Structural basis for the inhibitor recognition of human Lyn kinase domain. Bioorg. Med. Chem. Lett., 19 (23): 6557-60. [PMID:19857964]

17. 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]

18. Ren Y, Zheng J, Fan S, Wang L, Cheng M, Shi D, Zhang W, Tang R, Yu Y, Jiao L et al.. (2017) Anti-tumor efficacy of theliatinib in esophageal cancer patient-derived xenografts models with epidermal growth factor receptor (EGFR) overexpression and gene amplification. Oncotarget, 8 (31): 50832-50844. [PMID:28881608]

19. Saporito MS, Ochman AR, Lipinski CA, Handler JA, Reaume AG. (2012) MLR-1023 is a potent and selective allosteric activator of Lyn kinase in vitro that improves glucose tolerance in vivo. J. Pharmacol. Exp. Ther., 342 (1): 15-22. [PMID:22473614]

20. Tan L, Nomanbhoy T, Gurbani D, Patricelli M, Hunter J, Geng J, Herhaus L, Zhang J, Pauls E, Ham Y et al.. (2015) Discovery of Type II Inhibitors of TGFβ-Activated Kinase 1 (TAK1) and Mitogen-Activated Protein Kinase Kinase Kinase Kinase 2 (MAP4K2). J. Med. Chem., 58 (1): 183-96. [PMID:25075558]

21. Toubiana J, Rossi AL, Belaidouni N, Grimaldi D, Pene F, Chafey P, Comba B, Camoin L, Bismuth G, Claessens YE et al.. (2015) Src-family-tyrosine kinase Lyn is critical for TLR2-mediated NF-κB activation through the PI 3-kinase signaling pathway. Innate Immun, 21 (7): 685-97. [PMID:26055819]

22. 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]

How to cite this page

Src family: LYN proto-oncogene, Src family tyrosine kinase. Last modified on 26/04/2018. Accessed on 16/01/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2060.