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LIM domain kinase 2

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Target not currently curated in GtoImmuPdb

Target id: 2055

Nomenclature: LIM domain kinase 2

Abbreviated Name: LIMK2

Family: LIMK subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 638 22q12.2 LIMK2 LIM domain kinase 2
Mouse - 638 11 A1 Limk2 LIM domain kinase 2
Rat - 638 14q21 Limk2 LIM domain kinase 2
Previous and Unofficial Names Click here for help
LIM kinase 2 | Limk2a | Limk2b | Link2
Database Links Click here for help
Alphafold P53671 (Hs), O54785 (Mm), P53670 (Rn)
BRENDA 2.7.11.1
ChEMBL Target CHEMBL5932 (Hs)
Ensembl Gene ENSG00000182541 (Hs), ENSMUSG00000020451 (Mm), ENSRNOG00000019000 (Rn)
Entrez Gene 3985 (Hs), 16886 (Mm), 29524 (Rn)
Human Protein Atlas ENSG00000182541 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:3985 (Hs), mmu:16886 (Mm), rno:29524 (Rn)
OMIM 601988 (Hs)
Pharos P53671 (Hs)
RefSeq Nucleotide NM_001031801 (Hs), NM_010718 (Mm), NM_024135 (Rn)
RefSeq Protein NP_001026971 (Hs), NP_034848 (Mm), NP_077049 (Rn)
UniProtKB P53671 (Hs), O54785 (Mm), P53670 (Rn)
Wikipedia LIMK2 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Solution structures of the second LIM domain of human LIM-kinase 2 (LIMK2)
PDB Id:  1X6A
Resolution:  0.0Å
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 7.2 pKd 8
⤷ pKd 7.2 (Kd 6.3x10-8 M) [8]
compound 22m [PMID: 19831390] Small molecule or natural product Hs Inhibition 9.1 pIC50 2
⤷ pIC50 9.1 (IC50 8x10-10 M) [2]
compound 14 [PMID: 19831390] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.1 pIC50 2
⤷ pIC50 9.1 (IC50 9x10-10 M) [2]
compound 35 [PMID: 22902653] 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 8x10-9 M) [3]
LIMKi3 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.1 pIC50 4-6,9
⤷ pIC50 8.1 (IC50 8x10-9 M) [4-6,9]
compound 30 [PMID: 22902653] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.8 pIC50 3
⤷ pIC50 7.8 (IC50 1.6x10-8 M) [3]
compound 31 [PMID: 22902653] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.4 pIC50 3
⤷ pIC50 7.4 (IC50 3.8x10-8 M) [3]
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: 1,7
Key to terms and symbols Click column headers to sort
Target used in screen: LIMK2
Ligand Sp. Type Action Value Parameter
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.1 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.5 pKd
pazopanib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 6.4 pKd
Ki-20227 Small molecule or natural product Hs Inhibitor Inhibition 6.3 pKd
PLX-4720 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.2 pKd
crizotinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.2 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.0 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 5.8 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.8 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 5.7 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »

References

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1. 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]

2. 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]

3. 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]

4. 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]

5. 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]

6. 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]

7. 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]

8. 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]

9. 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 2. Last modified on 06/06/2019. Accessed on 11/09/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2055.