LIM domain kinase 1 | LIMK subfamily | IUPHAR/BPS Guide to PHARMACOLOGY

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LIM domain kinase 1

Target not currently curated in GtoImmuPdb

Target id: 2054

Nomenclature: LIM domain kinase 1

Abbreviated Name: LIMK1

Family: LIMK subfamily

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 - 647 7q11.23 LIMK1 LIM domain kinase 1
Mouse - 647 5 G2 Limk1 LIM-domain containing, protein kinase
Rat - 647 12 q12 Limk1 LIM domain kinase 1
Previous and Unofficial Names
LIM-domain containing, protein kinase | LIM-domain containing
Database Links
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
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
EC Number: 2.7.11.1

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
ZAK inhibitor 6p Hs Inhibition 7.6 pKd 12
pKd 7.6 (Kd 2.3x10-8 M) [12]
compound 14 [PMID: 19831390] Hs Inhibition 9.3 pIC50 4
pIC50 9.3 (IC50 5x10-10 M) [4]
RKI-1447 Hs Inhibition 8.8 pIC50 7
pIC50 8.8 (IC50 1.74x10-9 M) [7]
LIMKi3 Hs Inhibition 8.1 pIC50 8-10,14
pIC50 8.1 (IC50 7x10-9 M) [8-10,14]
voruciclib Hs Inhibition 7.7 pIC50 6
pIC50 7.7 (IC50 2.2x10-8 M) [6]
compound 30 [PMID: 22902653] Hs Inhibition 7.6 pIC50 5
pIC50 7.6 (IC50 2.3x10-8 M) [5]
compound 35 [PMID: 22902653] Hs Inhibition 7.5 pIC50 5
pIC50 7.5 (IC50 3x10-8 M) [5]
SR7826 Hs Inhibition 7.4 pIC50 13-14
pIC50 7.4 (IC50 4.3x10-8 M) [13-14]
compound 31 [PMID: 22902653] Hs Inhibition 7.2 pIC50 5
pIC50 7.2 (IC50 5.8x10-8 M) [5]
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: 2,11

Key to terms and symbols Click column headers to sort
Target used in screen: LIMK1
Ligand Sp. Type Action Value Parameter
staurosporine Hs Inhibitor Inhibition 6.3 pKd
dasatinib Hs Inhibitor Inhibition 6.2 pKd
tamatinib Hs Inhibitor Inhibition 6.2 pKd
foretinib Hs Inhibitor Inhibition 6.2 pKd
pazopanib Hs Inhibitor Inhibition 6.1 pKd
AST-487 Hs Inhibitor Inhibition 6.1 pKd
crizotinib Hs Inhibitor Inhibition 6.1 pKd
fedratinib Hs Inhibitor Inhibition 6.0 pKd
PD-173955 Hs Inhibitor Inhibition 6.0 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: 1,3

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 Hs Inhibitor Inhibition -0.6 5.0 2.0
staurosporine Hs Inhibitor Inhibition 5.5 1.5 1.5
K-252a Hs Inhibitor Inhibition 6.3 6.0 3.0
JNJ-7706621 Hs Inhibitor Inhibition 16.6 12.0 2.0
dasatinib Hs Inhibitor Inhibition 16.7
midostaurin Hs Inhibitor Inhibition 19.6 22.0 4.0
TWS119 Hs Inhibitor Inhibition 22.1 14.0 4.0
PDGF receptor tyrosine kinase inhibitor IV Hs Inhibitor Inhibition 23.3 13.0 2.0
tozasertib Hs Inhibitor Inhibition 33.1
Cdk2 inhibitor IV Hs Inhibitor Inhibition 35.2 39.0 10.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
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.. (2019) 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., [Epub ahead of print]. [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 13/12/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2054.