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CDC like kinase 2

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Target id: 1991

Nomenclature: CDC like kinase 2

Abbreviated Name: CLK2

Family: CLK family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 499 1q22 CLK2 CDC like kinase 2
Mouse - 499 3 F1 Clk2 CDC-like kinase 2
Rat - 500 2 q34 Clk2 CDC-like kinase 2
Previous and Unofficial Names Click here for help
dual specificity protein kinase CLK2
Database Links Click here for help
Alphafold P49760 (Hs), O35491 (Mm)
BRENDA 2.7.12.1
ChEMBL Target CHEMBL4225 (Hs), CHEMBL1075281 (Mm)
Ensembl Gene ENSG00000176444 (Hs), ENSMUSG00000068917 (Mm), ENSRNOG00000020500 (Rn)
Entrez Gene 1196 (Hs), 12748 (Mm), 365842 (Rn)
Human Protein Atlas ENSG00000176444 (Hs)
KEGG Enzyme 2.7.12.1
KEGG Gene hsa:1196 (Hs), mmu:12748 (Mm), rno:365842 (Rn)
OMIM 602989 (Hs)
Pharos P49760 (Hs)
RefSeq Nucleotide NM_003993 (Hs), NM_001163432 (Mm), NM_001014254 (Rn)
RefSeq Protein NP_003984 (Hs), NP_001156904 (Mm), NP_001014276 (Rn)
UniProtKB P49760 (Hs), O35491 (Mm)
Wikipedia CLK2 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Structure of human CDC2-like kinase 2 (CLK2)
PDB Id:  3NR9
Resolution:  2.89Å
Species:  Human
References: 
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
cirtuvivint Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.0 pIC50 6
⤷ pIC50 9.0 (IC50 1x10-9 M) [6]
rogocekib Small molecule or natural product Hs Inhibition 8.9 pIC50 11
⤷ pIC50 8.9 (IC50 1.4x10-9 M) [11]
lorecivivint Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.2 pIC50 5
⤷ pIC50 8.2 (IC50 5.8x10-9 M) [5]
compound 17 [PMID: 23642479] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.6 pIC50 3
⤷ pIC50 7.6 (IC50 2.3x10-8 M) [3]
Cdc2-like kinase inhibitor Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Mm Inhibition 6.7 pIC50 7
⤷ pIC50 6.7 (IC50 2x10-7 M) [7]
compound 3b [PMID: 23454515] Small molecule or natural product Click here for species-specific activity table Mm Inhibition 6.7 pIC50 2
⤷ pIC50 6.7 (IC50 2.1x10-7 M) [2]
ML315 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.6 pIC50 3
⤷ pIC50 6.6 (IC50 2.31x10-7 M) [3]
compound 20 [PMID: 30998356] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.6 pIC50 10
⤷ pIC50 6.6 (IC50 2.61x10-7 M) [10]
Description: Measuring in vitro enzyme inhibitory activity.
MW01 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.4 pIC50 9
⤷ pIC50 6.4 (IC50 3.6x10-7 M) [9]
Takinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.4 pIC50 12
⤷ pIC50 6.4 (IC50 4.3x10-7 M) [12]
MW05 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.8 pIC50 9
⤷ pIC50 5.8 (IC50 1.44x10-6 M) [9]
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: 4,13
Key to terms and symbols Click column headers to sort
Target used in screen: CLK2
Ligand Sp. Type Action Value Parameter
A-674563 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.3 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.1 pKd
GSK-1838705A Small molecule or natural product Hs Inhibitor Inhibition 7.8 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.7 pKd
TG-100-115 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.4 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.4 pKd
R547 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.1 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.1 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 7.0 pKd
SU-14813 Small molecule or natural product 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 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: CLK2/CLK2
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
JAK3 inhibitor VI Small molecule or natural product Hs Inhibitor Inhibition 0.3 1.0 1.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 3.7 1.0 1.0
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 3.8 -2.0 2.0
K-252a Small molecule or natural product Hs Inhibitor Inhibition 4.4 1.0 4.0
SU11274 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.1 7.0 2.0
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 10.0 8.0 3.0
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 13.6
PKCbeta inhibitor Small molecule or natural product Hs Inhibitor Inhibition 14.7 8.0 2.0
SU11652 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 15.8 9.0 1.0
aminopurvalanol A Small molecule or natural product Hs Inhibitor Inhibition 17.7 7.0 1.0
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. 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]

3. 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]

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. Deshmukh V, Hu H, Barroga C, Bossard C, Kc S, Dellamary L, Stewart J, Chiu K, Ibanez M, Pedraza M et al.. (2018) A small-molecule inhibitor of the Wnt pathway (SM04690) as a potential disease modifying agent for the treatment of osteoarthritis of the knee. Osteoarthr Cartil, 26 (1): 18-27. [PMID:28888902]

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, 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 USA, 104 (51): 20523-8. [PMID:18077363]

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. Mucka P, Lindemann P, Bosco B, Willenbrock M, Radetzki S, Neuenschwander M, Brischetto C, Peter von Kries J, Nazaré M, Scheidereit C. (2023) CLK2 and CLK4 are regulators of DNA damage-induced NF-κB targeted by novel small molecule inhibitors. Cell Chem Biol, 30 (10): 1303-1312.e3. [PMID:37506701]

10. Riggs JR, Elsner J, Cashion D, Robinson D, Tehrani L, Nagy M, Fultz KE, Krishna Narla R, Peng X, Tran T et al.. (2019) Design and Optimization Leading to an Orally Active TTK Protein Kinase Inhibitor with Robust Single Agent Efficacy. J Med Chem, 62 (9): 4401-4410. [PMID:30998356]

11. Tang J, Xie Y, Huang J, Zhang L, Jiang W, Li Z, Bian J. (2022) A critical update on the strategies towards small molecule inhibitors targeting Serine/arginine-rich (SR) proteins and Serine/arginine-rich proteins related kinases in alternative splicing. Bioorg Med Chem, 70: 116921. [PMID:35863237]

12. Totzke J, Gurbani D, Raphemot R, Hughes PF, Bodoor K, Carlson DA, Loiselle DR, Bera AK, Eibschutz LS, Perkins MM et al.. (2017) Takinib, a Selective TAK1 Inhibitor, Broadens the Therapeutic Efficacy of TNF-α Inhibition for Cancer and Autoimmune Disease. Cell Chem Biol, 24 (8): 1029-1039.e7. [PMID:28820959]

13. 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 2. Last modified on 06/03/2024. Accessed on 16/09/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=1991.