LIM domain kinase 2 | LIMK subfamily | IUPHAR/BPS Guide to PHARMACOLOGY

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LIM domain kinase 2

Target not currently curated in GtoImmuPdb

Target id: 2055

Nomenclature: LIM domain kinase 2

Abbreviated Name: LIMK2

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 - 686 22q12 LIMK2 LIM domain kinase 2
Mouse - 638 11 D Limk2 LIM motif-containing protein kinase 2
Rat - 638 14 q21 Limk2 LIM domain kinase 2
Previous and Unofficial Names
LIM kinase 2 | Limk2a | Limk2b | Link2
Database Links
BRENDA
ChEMBL Target
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:  Solution structures of the second LIM domain of human LIM-kinase 2 (LIMK2)
PDB Id:  1X6A
Resolution:  0.0Å
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 7.2 pKd 8
pKd 7.2 (Kd 6.3x10-8 M) [8]
compound 22m [PMID: 19831390] Hs Inhibition 9.1 pIC50 2
pIC50 9.1 (IC50 8x10-10 M) [2]
compound 14 [PMID: 19831390] Hs Inhibition 9.1 pIC50 2
pIC50 9.1 (IC50 9x10-10 M) [2]
compound 35 [PMID: 22902653] Hs Inhibition 8.1 pIC50 3
pIC50 8.1 (IC50 8x10-9 M) [3]
LIMKi3 Hs Inhibition 8.1 pIC50 4-6,9
pIC50 8.1 (IC50 8x10-9 M) [4-6,9]
compound 30 [PMID: 22902653] Hs Inhibition 7.8 pIC50 3
pIC50 7.8 (IC50 1.6x10-8 M) [3]
compound 31 [PMID: 22902653] Hs Inhibition 7.4 pIC50 3
pIC50 7.4 (IC50 3.8x10-8 M) [3]
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: 1,7

Key to terms and symbols Click column headers to sort
Target used in screen: LIMK2
Ligand Sp. Type Action Value Parameter
dasatinib Hs Inhibitor Inhibition 7.1 pKd
PD-173955 Hs Inhibitor Inhibition 6.5 pKd
pazopanib Hs Inhibitor Inhibition 6.4 pKd
Ki-20227 Hs Inhibitor Inhibition 6.3 pKd
PLX-4720 Hs Inhibitor Inhibition 6.2 pKd
crizotinib Hs Inhibitor Inhibition 6.2 pKd
NVP-TAE684 Hs Inhibitor Inhibition 6.0 pKd
tamatinib Hs Inhibitor Inhibition 5.8 pKd
foretinib Hs Inhibitor Inhibition 5.8 pKd
AST-487 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.. (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]. DOI: 10.1021/acs.jmedchem.9b00664 [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 23/10/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2055.