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CDC like kinase 3

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Target id: 1992

Nomenclature: CDC like kinase 3

Abbreviated Name: CLK3

Family: CLK family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 638 15q24.1 CLK3 CDC like kinase 3
Mouse - 638 9 B Clk3 CDC-like kinase 3
Rat - 490 8q24 Clk3 CDC-like kinase 3
Previous and Unofficial Names Click here for help
dual specificity protein kinase CLK3
Database Links Click here for help
Alphafold P49761 (Hs), O35492 (Mm), Q63117 (Rn)
BRENDA 2.7.12.1
ChEMBL Target CHEMBL4226 (Hs), CHEMBL1075282 (Mm)
Ensembl Gene ENSG00000179335 (Hs), ENSMUSG00000032316 (Mm), ENSRNOG00000030126 (Rn)
Entrez Gene 1198 (Hs), 102414 (Mm), 171305 (Rn)
Human Protein Atlas ENSG00000179335 (Hs)
KEGG Enzyme 2.7.12.1
KEGG Gene hsa:1198 (Hs), mmu:102414 (Mm), rno:171305 (Rn)
OMIM 602990 (Hs)
Pharos P49761 (Hs)
RefSeq Nucleotide NM_001130028 (Hs), NM_007713 (Mm), NM_134340 (Rn)
RefSeq Protein NP_001123500 (Hs), NP_031739 (Mm), NP_599167 (Rn)
SynPHARM 81087 (in complex with KH-CB19)
UniProtKB P49761 (Hs), O35492 (Mm), Q63117 (Rn)
Wikipedia CLK3 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of CLK3
PDB Id:  2EU9
Resolution:  1.53Å
Species:  Human
References:  2
Image of receptor 3D structure from RCSB PDB
Description:  CRYSTAL STRUCTURE OF THE HUMAN CLK3 IN COMPLEX WITH DKI
PDB Id:  2WU6
Resolution:  1.92Å
Species:  Human
References:  7
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of human CDC-like kinase 3 isoform in complex with leucettine L41
PDB Id:  3RAW
Ligand:  leucettine L41
Resolution:  2.09Å
Species:  Human
References:  5
Enzyme Reaction Click here for help
EC Number: 2.7.12.1

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
leucettine L41 Small molecule or natural product Click here for species-specific activity table Mm Inhibition 8.4 pIC50 5
⤷ pIC50 8.4 (IC50 4.5x10-9 M) [5]
cirtuvivint Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.9 pIC50 6
⤷ pIC50 7.9 (IC50 1.2x10-8 M) [6]
KH-CB19 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.3 pIC50 7
⤷ pIC50 6.3 (IC50 5.3x10-7 M) [7]
compound 3b [PMID: 23454515] Small molecule or natural product Click here for species-specific activity table Mm Inhibition 6.3 pIC50 3
⤷ pIC50 6.3 (IC50 5.5x10-7 M) [3]
View species-specific inhibitor tables
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: 4,9
Key to terms and symbols Click column headers to sort
Target used in screen: CLK3
Ligand Sp. Type Action Value Parameter
R547 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.9 pKd
A-674563 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.8 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.7 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.5 pKd
AT-7519 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.4 pKd
BI-2536 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.2 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.0 pKd
alvocidib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.8 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 5.7 pKd
MLN-8054 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.6 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: 1,8
Key to terms and symbols Click column headers to sort
Target used in screen: CLK3/CLK3
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 4.6 -4.0 -5.0
indirubin derivative E804 Small molecule or natural product Hs Inhibitor Inhibition 16.1 58.0 25.0
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 23.1 80.0 1.0
IRAK-1/4 inhibitor Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 24.1 55.0 56.0
Flt-3 inhibitor II Small molecule or natural product Hs Inhibitor Inhibition 24.8 69.0 4.0
GSK-3 inhibitor XIII Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 33.8 53.0 15.0
SP600125 Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 38.6 72.0 34.0
Gö 6983 Small molecule or natural product Hs Inhibitor Inhibition 43.6 59.0 45.0
EGFR/ErbB-2/ErbB-4 inhibitor Small molecule or natural product Hs Inhibitor Inhibition 47.1 83.0 125.0
indirubin-3'-monoxime Small molecule or natural product Hs Inhibitor Inhibition 48.2 79.0 54.0
Displaying the top 10 most potent ligands  View all ligands in screen »

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. Bullock AN, Das S, Debreczeni JE, Rellos P, Fedorov O, Niesen FH, Guo K, Papagrigoriou E, Amos AL, Cho S et al.. (2009) Kinase domain insertions define distinct roles of CLK kinases in SR protein phosphorylation. Structure, 17 (3): 352-62. [PMID:19278650]

3. Burgy G, Tahtouh T, Durieu E, Foll-Josselin B, Limanton E, Meijer L, Carreaux F, Bazureau JP. (2013) Chemical synthesis and biological validation of immobilized protein kinase inhibitory Leucettines. Eur J Med Chem, 62: 728-37. [PMID:23454515]

4. 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]

5. Debdab M, Carreaux F, Renault S, Soundararajan M, Fedorov O, Filippakopoulos P, Lozach O, Babault L, Tahtouh T, Baratte B et al.. (2011) Leucettines, a class of potent inhibitors of cdc2-like kinases and dual specificity, tyrosine phosphorylation regulated kinases derived from the marine sponge leucettamine B: modulation of alternative pre-RNA splicing. J Med Chem, 54 (12): 4172-86. [PMID:21615147]

6. Deshmukh V, O'Green AL, Bossard C, Barroga CF, Hood J. (2020) Methods of treating cartilage disorders through inhibition of clk and dyrk. Patent number: WO2020150552A2. Assignee: Samumed, Llc. Priority date: 17/01/2020. Publication date: 23/07/2020.

7. Fedorov O, Huber K, Eisenreich A, Filippakopoulos P, King O, Bullock AN, Szklarczyk D, Jensen LJ, Fabbro D, Trappe J et al.. (2011) Specific CLK inhibitors from a novel chemotype for regulation of alternative splicing. Chem Biol, 18 (1): 67-76. [PMID:21276940]

8. 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]

9. 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]

How to cite this page

CLK family: CDC like kinase 3. Last modified on 19/04/2023. Accessed on 03/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=1992.