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cyclin dependent kinase 5

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Target id: 1977

Nomenclature: cyclin dependent kinase 5

Abbreviated Name: CDK5

Family: CDK5 subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 292 7q36.1 CDK5 cyclin dependent kinase 5
Mouse - 292 5 11.73 cM Cdk5 cyclin dependent kinase 5
Rat - 292 4q11 Cdk5 cyclin-dependent kinase 5
Previous and Unofficial Names Click here for help
cell division protein kinase 5 | CR6 protein kinase | CRK6 | serine/threonine-protein kinase PSSALRE | tau protein kinase II catalytic subunit | TPKII catalytic subunit
Database Links Click here for help
Alphafold Q00535 (Hs), P49615 (Mm), Q03114 (Rn)
BRENDA 2.7.11.22
ChEMBL Target CHEMBL4036 (Hs), CHEMBL3885555 (Mm), CHEMBL5901 (Rn)
Ensembl Gene ENSG00000164885 (Hs), ENSMUSG00000028969 (Mm), ENSRNOG00000008017 (Rn)
Entrez Gene 1020 (Hs), 12568 (Mm), 140908 (Rn)
Human Protein Atlas ENSG00000164885 (Hs)
KEGG Enzyme 2.7.11.22
KEGG Gene hsa:1020 (Hs), mmu:12568 (Mm), rno:140908 (Rn)
OMIM 123831 (Hs)
Pharos Q00535 (Hs)
RefSeq Nucleotide NM_004935 (Hs), NM_007668 (Mm), NM_080885 (Rn)
RefSeq Protein NP_004926 (Hs), NP_031694 (Mm), NP_543161 (Rn)
SynPHARM 80334 (in complex with aloisine A)
UniProtKB Q00535 (Hs), P49615 (Mm), Q03114 (Rn)
Wikipedia CDK5 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  STRUCTURE AND REGULATION OF THE CDK5-P25(NCK5A) COMPLEX
PDB Id:  1H4L
Resolution:  2.65Å
Species:  Human
References:  22
Enzyme Reaction Click here for help
EC Number: 2.7.11.22

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
tanuxiciclib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.1 pIC50 3
⤷ pIC50 9.1 (IC50 7x10-10 M) [3]
Description: CDK5/p25
dinaciclib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 9.0 pIC50 15
⤷ pIC50 9.0 (IC50 1x10-9 M) [15]
zotiraciclib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.4 pIC50 9
⤷ pIC50 8.4 (IC50 4x10-9 M) [9]
RGB-286638 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.3 pIC50 4
⤷ pIC50 8.3 (IC50 5x10-9 M) [4]
Description: in association with regulatory subunit 1 (p35)cirs
purvalanol B Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.2 pIC50 10
⤷ pIC50 8.2 (IC50 6x10-9 M) [10]
Description: CDK5/p35 complex used in assay
AT-7519 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.9 pIC50 21
⤷ pIC50 7.9 (IC50 1.3x10-8 M) [21]
CDK inhibitor 4.35 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.8 pIC50 12
⤷ pIC50 7.8 (IC50 1.5x10-8 M) [12]
Description: Inhibition of CDK5/cyclin p25 complex.
aminopurvalanol A Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.7 pIC50 7
⤷ pIC50 7.7 (IC50 2x10-8 M) [7]
Description: CDK5 p35
SU9516 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.7 pIC50 13
⤷ pIC50 7.7 (IC50 2.2x10-8 M) [13]
Description: In vitro inhibition of CDK5/p25.
CGP74514A Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.6 pIC50 13
⤷ pIC50 7.6 (IC50 2.6x10-8 M) [13]
Description: In vitro inhibition of human CDK5/p25.
BS-194 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.5 pIC50 11
⤷ pIC50 7.5 (IC50 3x10-8 M) [11]
kinase inhibitor 2 [PMID: 30199702] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.3 pIC50 5
⤷ pIC50 7.3 (IC50 5x10-8 M) [5]
Description: CDK5/p25
purvalanol A Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.1 pIC50 10
⤷ pIC50 7.1 (IC50 7.5x10-8 M) [10]
Description: CDK5/p35 complex used in assay
GSK-3 inhibitor IX Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.1 pIC50 16,20
⤷ pIC50 7.1 (IC50 8.3x10-8 M) [16,20]
Description: CDK5/p25 complex
(R)-CR8 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.0 pIC50 2
⤷ pIC50 7.0 (IC50 1.1x10-7 M) [2]
Description: Inhibition of CDK5/p25 complex in vitro.
(S)-CR8 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.9 pIC50 2
⤷ pIC50 6.9 (IC50 1.2x10-7 M) [2]
Description: Inhibition of CDK5/p25 complex in vitro.
aloisine A Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.8 pIC50 17
⤷ pIC50 6.8 (IC50 1.6x10-7 M) [17]
Description: CDK5 p35
voruciclib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.7 pIC50 18
⤷ pIC50 6.7 (IC50 2.1x10-7 M) [18]
Description: Inhibition of CDK5/cyclin p35 (CDK5R1).
milciclib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.4 pIC50 13
⤷ pIC50 6.4 (IC50 3.83x10-7 M) [13]
Description: In vitro inhibition of CDK5/p25.
Cdk1/5 inhibitor Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 6.4 pIC50 7
⤷ pIC50 6.4 (IC50 4x10-7 M) [7]
Description: CDK5(p25)
kenpaullone Small molecule or natural product Primary target of this compound Bt Inhibition 6.1 pIC50 24
⤷ pIC50 6.1 (IC50 8.5x10-7 M) [24]
Description: CDK5/p25 complex
RO3306 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.6 pIC50 13
⤷ pIC50 5.6 (IC50 2.48x10-6 M) [13]
Description: In vitro inhibition of human CDK5/p25.
1-azakenpaullone Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.4 pIC50 14
⤷ pIC50 5.4 (IC50 4.2x10-6 M) [14]
Description: CDK5/p25 complex in assay
Cdk2 inhibitor IV Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 4.8 pIC50 19
⤷ pIC50 4.8 (IC50 1.5x10-5 M) [19]
Description: CDK5/p25 complex used in assay
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: 6,23
Key to terms and symbols Click column headers to sort
Target used in screen: CDK5
Ligand Sp. Type Action Value Parameter
R547 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.1 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.1 pKd
alvocidib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.0 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.4 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 6.3 pKd
AT-7519 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.2 pKd
BMS-387032 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.1 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.8 pKd
doramapimod Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 5.7 pKd
SB203580 Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition <5.5 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: CDK5-p25/CDK5-p25
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 0.1 1.0 0.0
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 0.2 -2.0 -1.0
JAK3 inhibitor VI Small molecule or natural product Hs Inhibitor Inhibition 1.5 1.0 0.0
JNJ-7706621 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 2.5 0.0 0.0
Cdk/Crk inhibitor Small molecule or natural product Hs Inhibitor Inhibition 2.5 0.0 -1.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 2.8 0.5 1.0
aminopurvalanol A Small molecule or natural product Hs Inhibitor Inhibition 3.3 13.0 1.0
purvalanol A Small molecule or natural product Hs Inhibitor Inhibition 3.9 0.0 0.0
SU9516 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 4.5 0.0 0.0
CGP74514A Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.2 1.0 0.0
Target used in screen: CDK5-p35/CDK5-p35
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
SU9516 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition -0.4 0.0 0.0
aminopurvalanol A Small molecule or natural product Hs Inhibitor Inhibition 0.1 20.0 2.0
JNJ-7706621 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 0.2 -1.0 0.0
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 0.9 1.0 -1.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 1.9 0.5 -0.5
purvalanol A Small molecule or natural product Hs Inhibitor Inhibition 2.6 1.0 0.0
alsterpaullone 2-cyanoethyl Small molecule or natural product Hs Inhibitor Inhibition 2.6 0.0 0.0
JAK3 inhibitor VI Small molecule or natural product Hs Inhibitor Inhibition 3.2 1.0 0.0
K-252a Small molecule or natural product Hs Inhibitor Inhibition 6.6 3.0 1.0
alsterpaullone Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.0 6.0 6.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Antigen presentation
Immuno Process:  Cellular signalling

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. Bettayeb K, Oumata N, Echalier A, Ferandin Y, Endicott JA, Galons H, Meijer L. (2008) CR8, a potent and selective, roscovitine-derived inhibitor of cyclin-dependent kinases. Oncogene, 27 (44): 5797-807. [PMID:18574471]

3. Changhee M, Oh B-g, Kim Y-e, Park C-m. (2016) Heterocyclic compound and pharmaceutical composition comprising same. Patent number: WO2016126085A2. Assignee: Beyond Bio. Priority date: 04/02/2015. Publication date: 03/11/2016.

4. Cirstea D, Hideshima T, Santo L, Eda H, Mishima Y, Nemani N, Hu Y, Mimura N, Cottini F, Gorgun G et al.. (2013) Small-molecule multi-targeted kinase inhibitor RGB-286638 triggers P53-dependent and -independent anti-multiple myeloma activity through inhibition of transcriptional CDKs. Leukemia, 27 (12): 2366-75. [PMID:23807770]

5. Compain G, Oumata N, Clarhaut J, Péraudeau E, Renoux B, Galons H, Papot S. (2018) A β-glucuronidase-responsive albumin-binding prodrug for potential selective kinase inhibitor-based cancer chemotherapy. Eur J Med Chem, 158: 1-6. [PMID:30199702]

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. 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. Goh KC, Novotny-Diermayr V, Hart S, Ong LC, Loh YK, Cheong A, Tan YC, Hu C, Jayaraman R, William AD et al.. (2012) TG02, a novel oral multi-kinase inhibitor of CDKs, JAK2 and FLT3 with potent anti-leukemic properties. Leukemia, 26 (2): 236-43. [PMID:21860433]

10. Gray NS, Wodicka L, Thunnissen AM, Norman TC, Kwon S, Espinoza FH, Morgan DO, Barnes G, LeClerc S, Meijer L et al.. (1998) Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors. Science, 281 (5376): 533-8. [PMID:9677190]

11. Heathcote DA, Patel H, Kroll SH, Hazel P, Periyasamy M, Alikian M, Kanneganti SK, Jogalekar AS, Scheiper B, Barbazanges M et al.. (2010) A novel pyrazolo[1,5-a]pyrimidine is a potent inhibitor of cyclin-dependent protein kinases 1, 2, and 9, which demonstrates antitumor effects in human tumor xenografts following oral administration. J Med Chem, 53 (24): 8508-22. [PMID:21080703]

12. Jorda R, Havlíček L, Šturc A, Tušková D, Daumová L, Alam M, Škerlová J, Nekardová M, Peřina M, Pospíšil T et al.. (2019) 3,5,7-Substituted Pyrazolo[4,3- d]pyrimidine Inhibitors of Cyclin-Dependent Kinases and Their Evaluation in Lymphoma Models. J Med Chem, 62 (9): 4606-4623. DOI: 10.1021/acs.jmedchem.9b00189 [PMID:30943029]

13. Jorda R, Hendrychová D, Voller J, Řezníčková E, Gucký T, Kryštof V. (2018) How Selective Are Pharmacological Inhibitors of Cell-Cycle-Regulating Cyclin-Dependent Kinases?. J Med Chem, 61 (20): 9105-9120. [PMID:30234987]

14. Kunick C, Lauenroth K, Leost M, Meijer L, Lemcke T. (2004) 1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta. Bioorg Med Chem Lett, 14 (2): 413-6. [PMID:14698171]

15. Martin MP, Olesen SH, Georg GI, Schönbrunn E. (2013) Cyclin-dependent kinase inhibitor dinaciclib interacts with the acetyl-lysine recognition site of bromodomains. ACS Chem Biol, 8 (11): 2360-5. [PMID:24007471]

16. Meijer L, Skaltsounis AL, Magiatis P, Polychronopoulos P, Knockaert M, Leost M, Ryan XP, Vonica CA, Brivanlou A, Dajani R et al.. (2003) GSK-3-selective inhibitors derived from Tyrian purple indirubins. Chem Biol, 10 (12): 1255-66. [PMID:14700633]

17. Mettey Y, Gompel M, Thomas V, Garnier M, Leost M, Ceballos-Picot I, Noble M, Endicott J, Vierfond JM, Meijer L. (2003) Aloisines, a new family of CDK/GSK-3 inhibitors. SAR study, crystal structure in complex with CDK2, enzyme selectivity, and cellular effects. J Med Chem, 46 (2): 222-36. [PMID:12519061]

18. Paiva C, Godbersen JC, Soderquist RS, Rowland T, Kilmarx S, Spurgeon SE, Brown JR, Srinivasa SP, Danilov AV. (2015) Cyclin-Dependent Kinase Inhibitor P1446A Induces Apoptosis in a JNK/p38 MAPK-Dependent Manner in Chronic Lymphocytic Leukemia B-Cells. PLoS ONE, 10 (11): e0143685. [PMID:26606677]

19. Pennati M, Campbell AJ, Curto M, Binda M, Cheng Y, Wang LZ, Curtin N, Golding BT, Griffin RJ, Hardcastle IR et al.. (2005) Potentiation of paclitaxel-induced apoptosis by the novel cyclin-dependent kinase inhibitor NU6140: a possible role for survivin down-regulation. Mol Cancer Ther, 4 (9): 1328-37. [PMID:16170024]

20. Polychronopoulos P, Magiatis P, Skaltsounis AL, Myrianthopoulos V, Mikros E, Tarricone A, Musacchio A, Roe SM, Pearl L, Leost M et al.. (2004) Structural basis for the synthesis of indirubins as potent and selective inhibitors of glycogen synthase kinase-3 and cyclin-dependent kinases. J Med Chem, 47 (4): 935-46. [PMID:14761195]

21. Squires MS, Feltell RE, Wallis NG, Lewis EJ, Smith DM, Cross DM, Lyons JF, Thompson NT. (2009) Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines. Mol Cancer Ther, 8 (2): 324-32. [PMID:19174555]

22. Tarricone C, Dhavan R, Peng J, Areces LB, Tsai LH, Musacchio A. (2001) Structure and regulation of the CDK5-p25(nck5a) complex. Mol Cell, 8 (3): 657-69. [PMID:11583627]

23. 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]

24. Zaharevitz DW, Gussio R, Leost M, Senderowicz AM, Lahusen T, Kunick C, Meijer L, Sausville EA. (1999) Discovery and initial characterization of the paullones, a novel class of small-molecule inhibitors of cyclin-dependent kinases. Cancer Res, 59 (11): 2566-9. [PMID:10363974]

How to cite this page

CDK5 subfamily: cyclin dependent kinase 5. Last modified on 04/02/2022. Accessed on 16/09/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=1977.