CDC like kinase 1 | CLK family | IUPHAR/BPS Guide to PHARMACOLOGY

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CDC like kinase 1

Target not currently curated in GtoImmuPdb

Target id: 1990

Nomenclature: CDC like kinase 1

Abbreviated Name: CLK1

Family: CLK family

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

Contents:

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 526 2q33 CLK1 CDC like kinase 1
Mouse - 483 1 C1.3 Clk1 CDC-like kinase 1
Rat - 483 9 q31 Clk1 CDC-like kinase 1
Previous and Unofficial Names
dual specificity protein kinase CLK1 | STY
Database Links
BRENDA 2.7.12.1
ChEMBL Target CHEMBL4224 (Hs), CHEMBL1075280 (Mm)
Ensembl Gene ENSG00000013441 (Hs), ENSMUSG00000026034 (Mm), ENSRNOG00000025768 (Rn)
Entrez Gene 1195 (Hs), 12747 (Mm), 301434 (Rn)
Human Protein Atlas ENSG00000013441 (Hs)
KEGG Enzyme 2.7.12.1
KEGG Gene hsa:1195 (Hs), mmu:12747 (Mm), rno:301434 (Rn)
OMIM 601951 (Hs)
RefSeq Nucleotide NM_001162407 (Hs), NM_001042634 (Mm), NM_001106913 (Rn)
RefSeq Protein NP_001155879 (Hs), NP_001036099 (Mm), NP_001100383 (Rn)
SynPHARM 81086 (in complex with KH-CB19)
UniProtKB P49759 (Hs), P22518 (Mm)
Wikipedia CLK1 (Hs)
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human CLK1 in complex with 10Z-Hymenialdisine
PDB Id:  1Z57
Resolution:  1.7Å
Species:  Human
References:  2
Enzyme Reaction
EC Number: 2.7.12.1

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
Cdc2-like kinase inhibitor Mm Inhibition 8.0 pKi 9
⤷ pKi 8.0 (Ki 1x10-8 M) [9]
leucettine L41 Mm Inhibition 10.8 pIC50 7
⤷ pIC50 10.8 (IC50 1.5x10-11 M) [7]
compound 17 [PMID: 23642479] Hs Inhibition 8.7 pIC50 5
⤷ pIC50 8.7 (IC50 2x10-9 M) [5]
KH-CB19 Hs Inhibition 7.7 pIC50 8
⤷ pIC50 7.7 (IC50 1.97x10-8 M) [8]
Cdc2-like kinase inhibitor Mm Inhibition 7.7 pIC50 9
⤷ pIC50 7.7 (IC50 2x10-8 M) [9]
compound 3b [PMID: 23454515] Mm Inhibition 7.2 pIC50 3
⤷ pIC50 7.2 (IC50 6.1x10-8 M) [3]
ML315 Hs Inhibition 7.2 pIC50 5
⤷ pIC50 7.2 (IC50 6.8x10-8 M) [5]
compound 2 [PMID: 22560567] Hs Inhibition 6.7 pIC50 4
⤷ pIC50 6.7 (IC50 2.1x10-7 M) [4]
View species-specific inhibitor tables
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: 6,10
Key to terms and symbols Click column headers to sort
Target used in screen: CLK1
Ligand Sp. Type Action Value Parameter
A-674563 Hs Inhibitor Inhibition 8.9 pKd
lestaurtinib Hs Inhibitor Inhibition 8.0 pKd
NVP-TAE684 Hs Inhibitor Inhibition 7.9 pKd
GSK-1838705A Hs Inhibitor Inhibition 7.7 pKd
sunitinib Hs Inhibitor Inhibition 7.7 pKd
staurosporine Hs Inhibitor Inhibition 7.5 pKd
KW-2449 Hs Inhibitor Inhibition 7.2 pKd
R547 Hs Inhibitor Inhibition 7.2 pKd
AST-487 Hs Inhibitor Inhibition 7.0 pKd
TG-100-115 Hs Inhibitor Inhibition 6.8 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
Key to terms and symbols Click column headers to sort
Target used in screen: nd/CLK1
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
K-252a Hs Inhibitor Inhibition 1.4
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 2.3
JAK3 inhibitor VI Hs Inhibitor Inhibition 4.1
staurosporine Hs Inhibitor Inhibition 11.9
PKR inhibitor Hs Inhibitor Inhibition 19.9
dorsomorphin Hs Inhibitor Inhibition 20.0
sunitinib Hs Inhibitor Inhibition 23.3
SU11652 Hs Inhibitor Inhibition 34.2
indirubin derivative E804 Hs Inhibitor Inhibition 36.6
Cdc2-like kinase inhibitor Hs Inhibitor Inhibition 41.8
Displaying the top 10 most potent ligands  View all ligands in screen »

References

Show »

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. Coffman K, Brodney M, Cook J, Lanyon L, Pandit J, Sakya S, Schachter J, Tseng-Lovering E, Wessel M. (2011) 6-amino-4-(pyrimidin-4-yl)pyridones: novel glycogen synthase kinase-3β inhibitors. Bioorg. Med. Chem. Lett., 21 (5): 1429-33. [PMID:21295469]

5. Coombs TC, Tanega C, Shen M, Wang JL, Auld DS, Gerritz SW, Schoenen FJ, Thomas CJ, Aubé J. (2013) Small-molecule pyrimidine inhibitors of the cdc2-like (Clk) and dual specificity tyrosine phosphorylation-regulated (Dyrk) kinases: development of chemical probe ML315. Bioorg. Med. Chem. Lett., 23 (12): 3654-61. [PMID:23642479]

6. 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]

7. 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]

8. 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]

9. Fedorov O, Marsden B, Pogacic V, Rellos P, Müller S, Bullock AN, Schwaller J, Sundström M, Knapp S. (2007) A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc. Natl. Acad. Sci. U.S.A., 104 (51): 20523-8. [PMID:18077363]

10. 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 1. Last modified on 29/01/2016. Accessed on 08/12/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1990.