cyclin-dependent kinase 5

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
BRENDA
Ensembl Gene
Entrez Gene
ExplorEnz
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG BRITE Hierarchy
KEGG Gene
OMIM
PhosphoSitePlus
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniProtKB
Wikipedia
Selected 3D Structures
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:  11
Enzyme Reaction
EC Number: 2.7.11.22
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
dinaciclib Hs Inhibition 9.0 pIC50 7
pIC50 9.0 (IC50 1x10-9 M) [7]
RGB-286638 Hs Inhibition 8.3 pIC50 2
pIC50 8.3 (IC50 5x10-9 M) [2]
Description: in association with regulatory subunit 1 (p35)cirs
purvalanol B Hs Inhibition 8.22 pIC50 6
pIC50 8.22 (IC50 6x10-9 M) [6]
Description: CDK5/p35 complex used in assay
aminopurvalanol A Hs Inhibition 7.7 pIC50 4
pIC50 7.7 (IC50 2x10-8 M) [4]
Description: CDK5 p35
purvalanol A Hs Inhibition 7.12 pIC50 6
pIC50 7.12 (IC50 7.5x10-8 M) [6]
Description: CDK5/p35 complex used in assay
GSK-3 inhibitor IX Hs Inhibition 7.08 pIC50 10
pIC50 7.08 (IC50 8.3x10-8 M) [10]
Description: CDK5/p25 complex
aloisine A Hs Inhibition 6.8 pIC50 8
pIC50 6.8 (IC50 1.6x10-7 M) [8]
Description: CDK5 p35
Cdk1/5 inhibitor Hs Inhibition 6.4 pIC50 4
pIC50 6.4 (IC50 4x10-7 M) [4]
Description: CDK5(p25)
kenpaullone Bt Inhibition 6.07 pIC50 13
pIC50 6.07 (IC50 8.5x10-7 M) [13]
Description: CDK5/p25 complex
Cdk2 inhibitor IV Hs Inhibition 4.82 pIC50 9
pIC50 4.82 (IC50 1.5x10-5 M) [9]
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.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 3,12

Key to terms and symbols Click column headers to sort
Target used in screen: CDK5
Ligand Sp. Type Action Affinity Units
R547 Hs Inhibitor Inhibition 8.13 pKd
staurosporine Hs Inhibitor Inhibition 7.08 pKd
alvocidib Hs Inhibitor Inhibition 6.96 pKd
lestaurtinib Hs Inhibitor Inhibition 6.39 pKd
AST-487 Hs Inhibitor Inhibition 6.26 pKd
AT-7519 Hs Inhibitor Inhibition 6.15 pKd
BMS-387032 Hs Inhibitor Inhibition 6.13 pKd
NVP-TAE684 Hs Inhibitor Inhibition 5.8 pKd
doramapimod Hs Inhibitor Inhibition 5.7 pKd
SB203580 Hs Inhibitor Inhibition <5.52 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: 1,5

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
aurora kinase/Cdk inhibitor 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
Cdk1 inhibitor (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
aurora kinase/Cdk inhibitor 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 »

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. 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. Leukemia27 (12): 2366-75. [PMID:23807770]

3. 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]

4. 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]

5. 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]

6. 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. Science281 (5376): 533-8. [PMID:9677190]

7. 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]

8. 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]

9. 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]

10. 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]

11. Tarricone C, Dhavan R, Peng J, Areces LB, Tsai LH, Musacchio A. (2001) Structure and regulation of the CDK5-p25(nck5a) complex. Mol. Cell8 (3): 657-69. [PMID:11583627]

12. 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]

13. 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 24/10/2014. Accessed on 19/12/2014. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1977.