cyclin dependent kinase 5 | CDK5 subfamily | IUPHAR/BPS Guide to PHARMACOLOGY

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cyclin dependent kinase 5

Target not currently curated in GtoImmuPdb

Target id: 1977

Nomenclature: cyclin dependent kinase 5

Abbreviated Name: CDK5

Family: CDK5 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 - 292 7q36 CDK5 cyclin dependent kinase 5
Mouse - 292 5 A3-B1 Cdk5 cyclin-dependent kinase 5
Rat - 292 4 q11 Cdk5 cyclin-dependent kinase 5
Previous and Unofficial Names
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
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
RefSeq Nucleotide
RefSeq Protein
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
PDB Id:  1H4L
Resolution:  2.65Å
Species:  Human
References:  21
Enzyme Reaction
EC Number:

Download all structure-activity data for this target as a CSV file

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
dinaciclib Hs Inhibition 9.0 pIC50 14
pIC50 9.0 (IC50 1x10-9 M) [14]
TG02 Hs Inhibition 8.4 pIC50 8
pIC50 8.4 (IC50 4x10-9 M) [8]
RGB-286638 Hs Inhibition 8.3 pIC50 3
pIC50 8.3 (IC50 5x10-9 M) [3]
Description: in association with regulatory subunit 1 (p35)cirs
purvalanol B Hs Inhibition 8.2 pIC50 9
pIC50 8.2 (IC50 6x10-9 M) [9]
Description: CDK5/p35 complex used in assay
AT-7519 Hs Inhibition 7.9 pIC50 20
pIC50 7.9 (IC50 1.3x10-8 M) [20]
CDK inhibitor 4.35 Hs Inhibition 7.8 pIC50 11
pIC50 7.8 (IC50 1.5x10-8 M) [11]
Description: Inhibition of CDK5/cyclin p25 complex.
aminopurvalanol A Hs Inhibition 7.7 pIC50 6
pIC50 7.7 (IC50 2x10-8 M) [6]
Description: CDK5 p35
SU9516 Hs Inhibition 7.7 pIC50 12
pIC50 7.7 (IC50 2.2x10-8 M) [12]
Description: In vitro inhibition of CDK5/p25.
CGP74514A Hs Inhibition 7.6 pIC50 12
pIC50 7.6 (IC50 2.6x10-8 M) [12]
Description: In vitro inhibition of human CDK5/p25.
BS-194 Hs Inhibition 7.5 pIC50 10
pIC50 7.5 (IC50 3x10-8 M) [10]
kinase inhibitor 2 [PMID: 30199702] Hs Inhibition 7.3 pIC50 4
pIC50 7.3 (IC50 5x10-8 M) [4]
Description: CDK5/p25
purvalanol A Hs Inhibition 7.1 pIC50 9
pIC50 7.1 (IC50 7.5x10-8 M) [9]
Description: CDK5/p35 complex used in assay
GSK-3 inhibitor IX Hs Inhibition 7.1 pIC50 15,19
pIC50 7.1 (IC50 8.3x10-8 M) [15,19]
Description: CDK5/p25 complex
(R)-CR8 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 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 Hs Inhibition 6.8 pIC50 16
pIC50 6.8 (IC50 1.6x10-7 M) [16]
Description: CDK5 p35
voruciclib Hs Inhibition 6.7 pIC50 17
pIC50 6.7 (IC50 2.1x10-7 M) [17]
Description: Inhibition of CDK5/cyclin p35 (CDK5R1).
milciclib Hs Inhibition 6.4 pIC50 12
pIC50 6.4 (IC50 3.83x10-7 M) [12]
Description: In vitro inhibition of CDK5/p25.
Cdk1/5 inhibitor Hs Inhibition 6.4 pIC50 6
pIC50 6.4 (IC50 4x10-7 M) [6]
Description: CDK5(p25)
kenpaullone Bt Inhibition 6.1 pIC50 23
pIC50 6.1 (IC50 8.5x10-7 M) [23]
Description: CDK5/p25 complex
RO3306 Hs Inhibition 5.6 pIC50 12
pIC50 5.6 (IC50 2.48x10-6 M) [12]
Description: In vitro inhibition of human CDK5/p25.
1-azakenpaullone Hs Inhibition 5.4 pIC50 13
pIC50 5.4 (IC50 4.2x10-6 M) [13]
Description: CDK5/p25 complex in assay
Cdk2 inhibitor IV Hs Inhibition 4.8 pIC50 18
pIC50 4.8 (IC50 1.5x10-5 M) [18]
Description: CDK5/p25 complex used in assay
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.
Reference: 5,22

Key to terms and symbols Click column headers to sort
Target used in screen: CDK5
Ligand Sp. Type Action Value Parameter
R547 Hs Inhibitor Inhibition 8.1 pKd
staurosporine Hs Inhibitor Inhibition 7.1 pKd
alvocidib Hs Inhibitor Inhibition 7.0 pKd
lestaurtinib Hs Inhibitor Inhibition 6.4 pKd
AST-487 Hs Inhibitor Inhibition 6.3 pKd
AT-7519 Hs Inhibitor Inhibition 6.2 pKd
BMS-387032 Hs Inhibitor Inhibition 6.1 pKd
NVP-TAE684 Hs Inhibitor Inhibition 5.8 pKd
doramapimod Hs Inhibitor Inhibition 5.7 pKd
SB203580 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
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.

Reference: 1,7

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 Hs Inhibitor Inhibition 0.1 1.0 0.0
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 0.2 -2.0 -1.0
JAK3 inhibitor VI Hs Inhibitor Inhibition 1.5 1.0 0.0
Cdk/Crk inhibitor Hs Inhibitor Inhibition 2.5 0.0 -1.0
JNJ-7706621 Hs Inhibitor Inhibition 2.5 0.0 0.0
staurosporine Hs Inhibitor Inhibition 2.8 0.5 1.0
aminopurvalanol A Hs Inhibitor Inhibition 3.3 13.0 1.0
purvalanol A Hs Inhibitor Inhibition 3.9 0.0 0.0
SU9516 Hs Inhibitor Inhibition 4.5 0.0 0.0
CGP74514A 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 Hs Inhibitor Inhibition -0.4 0.0 0.0
aminopurvalanol A Hs Inhibitor Inhibition 0.1 20.0 2.0
JNJ-7706621 Hs Inhibitor Inhibition 0.2 -1.0 0.0
PKR inhibitor Hs Inhibitor Inhibition 0.9 1.0 -1.0
staurosporine Hs Inhibitor Inhibition 1.9 0.5 -0.5
alsterpaullone 2-cyanoethyl Hs Inhibitor Inhibition 2.6 0.0 0.0
purvalanol A Hs Inhibitor Inhibition 2.6 1.0 0.0
JAK3 inhibitor VI Hs Inhibitor Inhibition 3.2 1.0 0.0
K-252a Hs Inhibitor Inhibition 6.6 3.0 1.0
alsterpaullone 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
GO Annotations:  Associated to 1 GO processes
GO:0048488 synaptic vesicle endocytosis TAS
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0031397 negative regulation of protein ubiquitination IEA


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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. 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]

4. 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]

5. 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]

6. 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]

7. 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]

8. 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]

9. 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]

10. 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]

11. 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]

12. 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]

13. 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]

14. 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]

15. 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]

16. 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]

17. 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]

18. 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]

19. 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]

20. 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]

21. 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]

22. 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]

23. 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 17/06/2020. Accessed on 13/08/2020. IUPHAR/BPS Guide to PHARMACOLOGY,