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LCK proto-oncogene, Src family tyrosine kinase

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 2053

Nomenclature: LCK proto-oncogene, Src family tyrosine kinase

Abbreviated Name: Lck

Family: Src family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 509 1p35.2 LCK LCK proto-oncogene, Src family tyrosine kinase
Mouse - 509 4 63.26 cM Lck lymphocyte protein tyrosine kinase
Rat - 509 5q36 Lck LCK proto-oncogene, Src family tyrosine kinase
Previous and Unofficial Names Click here for help
Hck-3 | Leukocyte C-terminal Src kinase | p56-LCK | Protein YT16 | lymphocyte-specific protein tyrosine kinase | LCK proto-oncogene
Database Links Click here for help
Alphafold P06239 (Hs), P06240 (Mm), Q01621 (Rn)
BRENDA 2.7.10.2
CATH/Gene3D 3.30.505.10
ChEMBL Target CHEMBL258 (Hs), CHEMBL2480 (Mm)
DrugBank Target P06239 (Hs)
Ensembl Gene ENSG00000182866 (Hs), ENSMUSG00000000409 (Mm), ENSRNOG00000009705 (Rn)
Entrez Gene 3932 (Hs), 16818 (Mm), 313050 (Rn)
Human Protein Atlas ENSG00000182866 (Hs)
KEGG Enzyme 2.7.10.2
KEGG Gene hsa:3932 (Hs), mmu:16818 (Mm), rno:313050 (Rn)
OMIM 153390 (Hs)
Orphanet ORPHA280151 (Hs)
Pharos P06239 (Hs)
RefSeq Nucleotide NM_001042771 (Hs), NM_001162432 (Mm), NM_001100709 (Rn)
RefSeq Protein NP_001036236 (Hs), NP_001155904 (Mm), NP_001094179 (Rn)
SynPHARM 84043 (in complex with PP2)
UniProtKB P06239 (Hs), P06240 (Mm), Q01621 (Rn)
Wikipedia LCK (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  LCK complexed with a pyrazolopyrimidine
PDB Id:  3MPM
Resolution:  1.95Å
Species:  Human
References:  16
Image of receptor 3D structure from RCSB PDB
Description:  FREE P56LCK SH2 DOMAIN
PDB Id:  1BHH
Resolution:  1.9Å
Species:  Human
References:  35
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
belizatinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.6 pKd 22
⤷ pKd 7.6 (Kd 2.8x10-8 M) [22]
Description: Binding affinity in vitro.
ZAK inhibitor 6p Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.8 pKd 39
⤷ pKd 6.8 (Kd 1.6x10-7 M) [39]
DDR1/2 inhibitor 5n Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.7 pKd 36
⤷ pKd 6.7 (Kd 1.8x10-7 M) [36]
neolymphostin A Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.3 pKd 8
⤷ pKd 5.3 (Kd 4.6x10-6 M) [8]
acalabrutinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition <6.0 pEC50 4
⤷ pEC50 <6.0 (EC50 >1x10-6 M) [4]
eCF506 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition >9.3 pIC50 12
⤷ pIC50 >9.3 (IC50 <5x10-10 M) [12]
Lck inhibitor Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition >9.0 pIC50 6
⤷ pIC50 >9.0 (IC50 <1x10-9 M) [6]
compound 2 [PMID: 15546730] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.0 pIC50 9
⤷ pIC50 9.0 (IC50 1x10-9 M) [9]
WH-4-023 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.7 pIC50 27
⤷ pIC50 8.7 (IC50 2x10-9 M) [27]
CCT241161 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.5 pIC50 14
⤷ pIC50 8.5 (IC50 3x10-9 M) [14]
saracatinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition >8.4 pIC50 18
⤷ pIC50 >8.4 (IC50 <4x10-9 M) [18]
PP2 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.4 pIC50 17
⤷ pIC50 8.4 (IC50 4x10-9 M) [17]
compound 30 [PMID: 17280833] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.3 pIC50 11
⤷ pIC50 8.3 (IC50 5x10-9 M) [11]
PP1 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.3 pIC50 17
⤷ pIC50 8.3 (IC50 5x10-9 M) [17]
nefextinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.3 pIC50 38
⤷ pIC50 8.3 (IC50 5.5x10-9 M) [38]
ibrutinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.2 pIC50 7
⤷ pIC50 8.2 (IC50 6.3x10-9 M) [7]
compound 23 [PMID: 17600705] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.1 pIC50 3
⤷ pIC50 8.1 (IC50 8.5x10-9 M) [3]
dorsomorphin Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.8 pIC50 25
⤷ pIC50 7.8 (IC50 1.6x10-8 M) [25]
Description: Assayed using AMPK heterotrimeric complex containing α2, β1, γ1 subunits
CCT196969 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.7 pIC50 14
⤷ pIC50 7.7 (IC50 2x10-8 M) [14]
compound 7 [PMID: 22464456] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.4 pIC50 28
⤷ pIC50 7.4 (IC50 3.92x10-8 M) [28]
7-hydroxystaurosporine Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.3 pIC50 19
⤷ pIC50 7.3 (IC50 5x10-8 M) [19]
JNJ-28312141 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.1 pIC50 26
⤷ pIC50 7.1 (IC50 8.8x10-8 M) [26]
SU6656 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.8 pIC50 2
⤷ pIC50 6.8 (IC50 1.5x10-7 M) [2]
xiliertinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.8 pIC50 30
⤷ pIC50 6.8 (IC50 1.76x10-7 M) [30]
compound 19a [PMID: 21855335] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.7 pIC50 40
⤷ pIC50 6.7 (IC50 1.8x10-7 M) [40]
compound 36 [PMID: 21958547] Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.1 pIC50 20
⤷ pIC50 6.1 (IC50 7.72x10-7 M) [20]
pexidartinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.1 pIC50 34
⤷ pIC50 6.1 (IC50 8.6x10-7 M) [34]
TAK-020 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.0 pIC50 31
⤷ pIC50 6.0 (IC50 1x10-6 M) [31]
GSK2646264 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 5.4 pIC50 5
⤷ pIC50 5.4 (IC50 3.981x10-6 M) [5]
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: 10,37
Key to terms and symbols Click column headers to sort
Target used in screen: LCK
Ligand Sp. Type Action Value Parameter
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 9.7 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 9.2 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.0 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.2 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 8.0 pKd
vandetanib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.8 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.5 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.5 pKd
crizotinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.5 pKd
masitinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.5 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: 1,13
Key to terms and symbols Click column headers to sort
Target used in screen: Lck activated
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
Lck inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition -3.0 2.0
Src kinase inhibitor I Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition -2.0 0.0
tivozanib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition -2.0 1.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition -1.5 0.0
PDGF RTK inhibitor Small molecule or natural product Hs Inhibitor Inhibition 0.0 0.0
GSK-3 inhibitor IX Small molecule or natural product Hs Inhibitor Inhibition 1.0 19.0
TWS119 Small molecule or natural product Hs Inhibitor Inhibition 4.0 0.0
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 5.0 6.0
indirubin derivative E804 Small molecule or natural product Hs Inhibitor Inhibition 5.0 8.0
K-252a Small molecule or natural product Hs Inhibitor Inhibition 6.0 8.0
Target used in screen: Lck/LCK
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 0.3
Lck inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 1.1 1.0 -1.0
PDGF RTK inhibitor Small molecule or natural product Hs Inhibitor Inhibition 1.6 1.0 -1.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 1.8 -0.5 4.5
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 1.9
vandetanib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 3.6
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 4.7
Src kinase inhibitor I Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 4.7 0.0 -1.0
masitinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.6
SU11652 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 11.8 12.0 2.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
Phosphorylation and activation of Lck is an early and critical step in pre-TCR (T cell receptor) and TCR signalling. Activated Lck phosphorylates immunoreceptor tyrosine-based activation motifs of the ζ chain of the TCR leading to recruitment and activation of ZAP-70 tyrosine kinase, and activation of downstream MAPKs and NF-κB. TCR-based signals are required at several stages of T-cell development and it is thought that Lck is the major contributor to TCR signal transduction (with the related Src tyrosine kinase Fyn also playing a role) [29]. JNK pathway-associated phosphatase (JKAP or JSP-1) is reported to dephosphorylate Lck and attenuate TCR signalling [23], with the likelihood that this mechanism would suppressT-cell-mediated immunity and autoimmunity.
Cell Type Associations
Immuno Cell Type:  T cells
References:  24
Immuno Cell Type:  Natural killer cells
Cell Ontology Term:   natural killer cell (CL:0000623)
References:  24
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  T cell (activation)
Immuno Process:  Immune regulation
Immuno Process:  Immune system development
Immuno Process:  Chemotaxis & migration
Immuno Process:  Cellular signalling
Physiological Functions Comments
Lck is required for the T cell receptor (TCR)-mediated signalling underlying normal T cell development and activation [15,21,32-33]. Selective inhibition of Lck offers a new strategy for the treatment of graft rejection and/or T cell-mediated autoimmune and inflammatory disease (eg rheumatoid arthritis, psoriasis, multiple sclerosis, atherosclerosis).
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Severe combined immunodeficiency due to LCK deficiency
Synonyms: Immunodeficiency 22; IMD22 [OMIM: 615758]
OMIM: 615758
Orphanet: ORPHA280142

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. Bain J, Plater L, Elliott M, Shpiro N, Hastie CJ, McLauchlan H, Klevernic I, Arthur JS, Alessi DR, Cohen P. (2007) The selectivity of protein kinase inhibitors: a further update. Biochem J, 408 (3): 297-315. [PMID:17850214]

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. Barker MD, Liddle J, Atkinson FL, Wilson DM, Dickson MC, Ramirez-Molina C, Lewis H, Davis RP, Somers DO, Neu M et al.. (2018) Discovery of potent and selective Spleen Tyrosine Kinase inhibitors for the topical treatment of inflammatory skin disease. Bioorg Med Chem Lett, 28 (21): 3458-3462. [PMID:30249354]

6. Burchat AF, Calderwood DJ, Hirst GC, Holman NJ, Johnston DN, Munschauer R, Rafferty P, Tometzki GB. (2000) Pyrrolo[2,3-d]pyrimidines containing an extended 5-substituent as potent and selective inhibitors of lck II. Bioorg Med Chem Lett, 10 (19): 2171-4. [PMID:11012022]

7. 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]

8. Castro-Falcón G, Seiler GS, Demir Ö, Rathinaswamy MK, Hamelin D, Hoffmann RM, Makowski SL, Letzel AC, Field SJ, Burke JE et al.. (2018) Neolymphostin A Is a Covalent Phosphoinositide 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Dual Inhibitor That Employs an Unusual Electrophilic Vinylogous Ester. J Med Chem, 61 (23): 10463-10472. [PMID:30380865]

9. Chen P, Norris D, Das J, Spergel SH, Wityak J, Leith L, Zhao R, Chen BC, Pitt S, Pang S et al.. (2004) Discovery of novel 2-(aminoheteroaryl)-thiazole-5-carboxamides as potent and orally active Src-family kinase p56(Lck) inhibitors. Bioorg Med Chem Lett, 14 (24): 6061-6. [PMID:15546730]

10. 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]

11. DiMauro EF, Newcomb J, Nunes JJ, Bemis JE, Boucher C, Buchanan JL, Buckner WH, Cheng A, Faust T, Hsieh F et al.. (2007) Discovery of 4-amino-5,6-biaryl-furo[2,3-d]pyrimidines as inhibitors of Lck: development of an expedient and divergent synthetic route and preliminary SAR. Bioorg Med Chem Lett, 17 (8): 2305-9. [PMID:17280833]

12. 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]

13. 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]

14. Girotti MR, Lopes F, Preece N, Niculescu-Duvaz D, Zambon A, Davies L, Whittaker S, Saturno G, Viros A, Pedersen M et al.. (2015) Paradox-breaking RAF inhibitors that also target SRC are effective in drug-resistant BRAF mutant melanoma. Cancer Cell, 27 (1): 85-96. [PMID:25500121]

15. Goldman FD, Ballas ZK, Schutte BC, Kemp J, Hollenback C, Noraz N, Taylor N. (1998) Defective expression of p56lck in an infant with severe combined immunodeficiency. J Clin Invest, 102 (2): 421-9. [PMID:9664084]

16. Gommermann N, Buehlmayer P, von Matt A, Breitenstein W, Masuya K, Pirard B, Furet P, Cowan-Jacob SW, Weckbecker G. (2010) New pyrazolo[1,5a]pyrimidines as orally active inhibitors of Lck. Bioorg Med Chem Lett, 20 (12): 3628-31. [PMID:20483608]

17. Hanke JH, Gardner JP, Dow RL, Changelian PS, Brissette WH, Weringer EJ, Pollok BA, Connelly PA. (1996) Discovery of a novel, potent, and Src family-selective tyrosine kinase inhibitor. Study of Lck- and FynT-dependent T cell activation. J Biol Chem, 271 (2): 695-701. [PMID:8557675]

18. Hennequin LF, Allen J, Breed J, Curwen J, Fennell M, Green TP, Lambert-van der Brempt C, Morgentin R, Norman RA, Olivier A et al.. (2006) N-(5-chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5- (tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine, a novel, highly selective, orally available, dual-specific c-Src/Abl kinase inhibitor. J Med Chem, 49 (22): 6465-88. [PMID:17064066]

19. Jiang X, Zhao B, Britton R, Lim LY, Leong D, Sanghera JS, Zhou BB, Piers E, Andersen RJ, Roberge M. (2004) Inhibition of Chk1 by the G2 DNA damage checkpoint inhibitor isogranulatimide. Mol Cancer Ther, 3 (10): 1221-7. [PMID:15486189]

20. 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]

21. Levin SD, Anderson SJ, Forbush KA, Perlmutter RM. (1993) A dominant-negative transgene defines a role for p56lck in thymopoiesis. EMBO J, 12 (4): 1671-80. [PMID:8385609]

22. Lewis RT, Bode CM, Choquette DM, Potashman M, Romero K, Stellwagen JC, Teffera Y, Moore E, Whittington DA, Chen H et al.. (2012) The discovery and optimization of a novel class of potent, selective, and orally bioavailable anaplastic lymphoma kinase (ALK) inhibitors with potential utility for the treatment of cancer. J Med Chem, 55 (14): 6523-40. [PMID:22734674]

23. Li JP, Yang CY, Chuang HC, Lan JL, Chen DY, Chen YM, Wang X, Chen AJ, Belmont JW, Tan TH. (2014) The phosphatase JKAP/DUSP22 inhibits T-cell receptor signalling and autoimmunity by inactivating Lck. Nat Commun, 5: 3618. [PMID:24714587]

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

25. Machrouhi F, Ouhamou N, Laderoute K, Calaoagan J, Bukhtiyarova M, Ehrlich PJ, Klon AE. (2010) The rational design of a novel potent analogue of the 5'-AMP-activated protein kinase inhibitor compound C with improved selectivity and cellular activity. Bioorg Med Chem Lett, 20 (22): 6394-9. [PMID:20932747]

26. Manthey CL, Johnson DL, Illig CR, Tuman RW, Zhou Z, Baker JF, Chaikin MA, Donatelli RR, Franks CF, Zeng L et al.. (2009) JNJ-28312141, a novel orally active colony-stimulating factor-1 receptor/FMS-related receptor tyrosine kinase-3 receptor tyrosine kinase inhibitor with potential utility in solid tumors, bone metastases, and acute myeloid leukemia. Mol Cancer Ther, 8 (11): 3151-61. [PMID:19887542]

27. Martin MW, Newcomb J, Nunes JJ, McGowan DC, Armistead DM, Boucher C, Buchanan JL, Buckner W, Chai L, Elbaum D et al.. (2006) Novel 2-aminopyrimidine carbamates as potent and orally active inhibitors of Lck: synthesis, SAR, and in vivo antiinflammatory activity. J Med Chem, 49 (16): 4981-91. [PMID:16884310]

28. 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]

29. Palacios EH, Weiss A. (2004) Function of the Src-family kinases, Lck and Fyn, in T-cell development and activation. Oncogene, 23 (48): 7990-8000. [PMID:15489916]

30. 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]

31. Sabat M, Dougan DR, Knight B, Lawson JD, Scorah N, Smith CR, Taylor ER, Vu P, Wyrick C, Wang H et al.. (2021) Discovery of the Bruton's Tyrosine Kinase Inhibitor Clinical Candidate TAK-020 (S)-5-(1-((1-Acryloylpyrrolidin-3-yl)oxy)isoquinolin-3-yl)-2,4-dihydro-3H-1,2,4-triazol-3-one, by Fragment-Based Drug Design. J Med Chem, 64 (17): 12893-12902. [PMID:34448571]

32. Seddon B, Zamoyska R. (2002) TCR signals mediated by Src family kinases are essential for the survival of naive T cells. J Immunol, 169 (6): 2997-3005. [PMID:12218114]

33. Straus DB, Weiss A. (1992) Genetic evidence for the involvement of the lck tyrosine kinase in signal transduction through the T cell antigen receptor. Cell, 70 (4): 585-93. [PMID:1505025]

34. Tap WD, Wainberg ZA, Anthony SP, Ibrahim PN, Zhang C, Healey JH, Chmielowski B, Staddon AP, Cohn AL, Shapiro GI et al.. (2015) Structure-Guided Blockade of CSF1R Kinase in Tenosynovial Giant-Cell Tumor. N Engl J Med, 373 (5): 428-37. [PMID:26222558]

35. Tong L, Warren TC, Lukas S, Schembri-King J, Betageri R, Proudfoot JR, Jakes S. (1998) Carboxymethyl-phenylalanine as a replacement for phosphotyrosine in SH2 domain binding. J Biol Chem, 273 (32): 20238-42. [PMID:9685372]

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Src family: LCK proto-oncogene, Src family tyrosine kinase. Last modified on 06/03/2024. Accessed on 20/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2053.