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LIM domain kinase 1

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Target not currently curated in GtoImmuPdb

Target id: 2054

Nomenclature: LIM domain kinase 1

Abbreviated Name: LIMK1

Family: LIMK subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 647 7q11.23 LIMK1 LIM domain kinase 1
Mouse - 647 5 G2 Limk1 LIM domain kinase 1
Rat - 647 12q12 Limk1 LIM domain kinase 1
Previous and Unofficial Names Click here for help
LIM-domain containing, protein kinase | LIM-domain containing
Database Links Click here for help
Alphafold P53667 (Hs), P53668 (Mm), P53669 (Rn)
BRENDA 2.7.11.1
ChEMBL Target CHEMBL3836 (Hs), CHEMBL3407314 (Rn)
Ensembl Gene ENSG00000106683 (Hs), ENSMUSG00000029674 (Mm), ENSRNOG00000001470 (Rn)
Entrez Gene 3984 (Hs), 16885 (Mm), 65172 (Rn)
Human Protein Atlas ENSG00000106683 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:3984 (Hs), mmu:16885 (Mm), rno:65172 (Rn)
OMIM 601329 (Hs)
Orphanet ORPHA123060 (Hs)
Pharos P53667 (Hs)
RefSeq Nucleotide NM_001204426 (Hs), NM_010717 (Mm), NM_031727 (Rn)
RefSeq Protein NP_002305 (Hs), NP_034847 (Mm), NP_113915 (Rn)
UniProtKB P53667 (Hs), P53668 (Mm), P53669 (Rn)
Wikipedia LIMK1 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the human LIMK1 kinase domain in complex with staurosporine
PDB Id:  3S95
Resolution:  1.65Å
Species:  Human
References: 
Enzyme Reaction Click here for help
EC Number: 2.7.11.1

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
ZAK inhibitor 6p Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.6 pKd 12
⤷ pKd 7.6 (Kd 2.3x10-8 M) [12]
compound 14 [PMID: 19831390] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.3 pIC50 4
⤷ pIC50 9.3 (IC50 5x10-10 M) [4]
RKI-1447 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.8 pIC50 7
⤷ pIC50 8.8 (IC50 1.74x10-9 M) [7]
LIMKi3 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.1 pIC50 8-10,14
⤷ pIC50 8.1 (IC50 7x10-9 M) [8-10,14]
voruciclib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.7 pIC50 6
⤷ pIC50 7.7 (IC50 2.2x10-8 M) [6]
compound 30 [PMID: 22902653] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.6 pIC50 5
⤷ pIC50 7.6 (IC50 2.3x10-8 M) [5]
compound 35 [PMID: 22902653] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.5 pIC50 5
⤷ pIC50 7.5 (IC50 3x10-8 M) [5]
SR7826 Small molecule or natural product Hs Inhibition 7.4 pIC50 13-14
⤷ pIC50 7.4 (IC50 4.3x10-8 M) [13-14]
compound 31 [PMID: 22902653] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.2 pIC50 5
⤷ pIC50 7.2 (IC50 5.8x10-8 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: 2,11
Key to terms and symbols Click column headers to sort
Target used in screen: LIMK1
Ligand Sp. Type Action Value Parameter
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.3 pKd
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.2 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.2 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.2 pKd
pazopanib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 6.1 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 6.1 pKd
crizotinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.1 pKd
fedratinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.0 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.0 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: 1,3
Key to terms and symbols Click column headers to sort
Target used in screen: LIMK1/LIMK1
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition -0.6 5.0 2.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.5 1.5 1.5
K-252a Small molecule or natural product Hs Inhibitor Inhibition 6.3 6.0 3.0
JNJ-7706621 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 16.6 12.0 2.0
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 16.7
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 19.6 22.0 4.0
TWS119 Small molecule or natural product Hs Inhibitor Inhibition 22.1 14.0 4.0
PDGF receptor tyrosine kinase inhibitor IV Small molecule or natural product Hs Inhibitor Inhibition 23.3 13.0 2.0
tozasertib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 33.1
Cdk2 inhibitor IV Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 35.2 39.0 10.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Immune regulation
Immuno Process:  Cellular signalling
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Williams-Beuren syndrome
Synonyms: Williams syndrome [Orphanet: ORPHA904]
Disease Ontology: DOID:1928
OMIM: 194050
Orphanet: ORPHA904

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. 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]

3. 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]

4. Harrison BA, Whitlock NA, Voronkov MV, Almstead ZY, Gu KJ, Mabon R, Gardyan M, Hamman BD, Allen J, Gopinathan S et al.. (2009) Novel class of LIM-kinase 2 inhibitors for the treatment of ocular hypertension and associated glaucoma. J Med Chem, 52 (21): 6515-8. [PMID:19831390]

5. He L, Seitz SP, Trainor GL, Tortolani D, Vaccaro W, Poss M, Tarby CM, Tokarski JS, Penhallow B, Hung CY et al.. (2012) Modulation of cofilin phosphorylation by inhibition of the Lim family kinases. Bioorg Med Chem Lett, 22 (18): 5995-8. [PMID:22902653]

6. Paiva C, Godbersen JC, Soderquist RS, Rowland T, Kilmarx S, Spurgeon SE, Brown JR, Srinivasa SP, Danilov AV. (2015) Cyclin-Dependent Kinase Inhibitor P1446A Induces Apoptosis in a JNK/p38 MAPK-Dependent Manner in Chronic Lymphocytic Leukemia B-Cells. PLoS ONE, 10 (11): e0143685. [PMID:26606677]

7. Pireddu R, Forinash KD, Sun NN, Martin MP, Sung SS, Alexander B, Zhu JY, Guida WC, Schönbrunn E, Sebti SM et al.. (2012) Pyridylthiazole-based ureas as inhibitors of Rho associated protein kinases (ROCK1 and 2). Medchemcomm, 3 (6): 699-709. [PMID:23275831]

8. Ross-Macdonald P, de Silva H, Guo Q, Xiao H, Hung CY, Penhallow B, Markwalder J, He L, Attar RM, Lin TA et al.. (2008) Identification of a nonkinase target mediating cytotoxicity of novel kinase inhibitors. Mol Cancer Ther, 7 (11): 3490-8. [PMID:19001433]

9. Scott RW, Hooper S, Crighton D, Li A, König I, Munro J, Trivier E, Wickman G, Morin P, Croft DR et al.. (2010) LIM kinases are required for invasive path generation by tumor and tumor-associated stromal cells. J Cell Biol, 191 (1): 169-85. [PMID:20876278]

10. Sparrow N, Manetti ME, Bott M, Fabianac T, Petrilli A, Bates ML, Bunge MB, Lambert S, Fernandez-Valle C. (2012) The actin-severing protein cofilin is downstream of neuregulin signaling and is essential for Schwann cell myelination. J Neurosci, 32 (15): 5284-97. [PMID:22496574]

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. Yang J, Shibu MA, Kong L, Luo J, BadrealamKhan F, Huang Y, Tu ZC, Yun CH, Huang CY, Ding K et al.. (2020) Design, Synthesis, and Structure-Activity Relationships of 1,2,3-Triazole Benzenesulfonamides as New Selective Leucine-Zipper and Sterile-α Motif Kinase (ZAK) Inhibitors. J Med Chem, 63 (5): 2114-2130. [PMID:31244114]

13. Yin Y, Zheng K, Eid N, Howard S, Jeong JH, Yi F, Guo J, Park CM, Bibian M, Wu W et al.. (2015) Bis-aryl urea derivatives as potent and selective LIM kinase (Limk) inhibitors. J Med Chem, 58 (4): 1846-61. [PMID:25621531]

14. Yu Q, Gratzke C, Wang Y, Herlemann A, Sterr CM, Rutz B, Ciotkowska A, Wang X, Strittmatter F, Stief CG et al.. (2018) Inhibition of human prostate smooth muscle contraction by the LIM kinase inhibitors, SR7826 and LIMKi3. Br J Pharmacol, 175 (11): 2077-2096. [PMID:29574791]

How to cite this page

LIMK subfamily: LIM domain kinase 1. Last modified on 06/06/2019. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2054.