Target Information

Target General Infomation
Target ID
T20973
Former ID
TTDR00296
Target Name
Cell division protein kinase 5
Gene Name
CDK5
Synonyms
Cyclin-dependent kinase 5; Cyclin-dependent kinase 5 (CDK5); PDPK; Proline-directed protein kinase 33 kDa subunit; Proline-directed protein kinase F(A) (PDPK F(A)); Serine/threonine protein kinase PSSALRE; Serine/threonine-protein kinase PSSALRE; TPKII catalytic subunit; Tau protein kinase II catalytic subunit; CDK5
Target Type
Discontinued
Function
Proline-directed serine/threonine-protein kinase essential for neuronal cell cycle arrest and differentiation and may be involved in apoptotic cell death in neuronal diseases by triggering abortive cell cycle re-entry. Interacts with D1 and D3- type G1 cyclins. Phosphorylates SRC, NOS3, VIM/vimentin, p35/CDK5R1, MEF2A, SIPA1L1, SH3GLB1, PXN, PAK1, MCAM/MUC18, SEPT5, SYN1, DNM1, AMPH, SYNJ1, CDK16, RAC1, RHOA, CDC42, TONEBP/NFAT5, MAPT/TAU, MAP1B, histone H1, p53/TP53, HDAC1, APEX1, PTK2/FAK1, huntingtin/HTT, ATM, MAP2, NEFH and NEFM. Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission, by phosphorylating key proteins.
BioChemical Class
Kinase
Target Validation
T20973
UniProt ID
Q00535
EC Number
EC 2.7.11.22
Sequence
MQKYEKLEKIGEGTYGTVFKAKNRETHEIVALKRVRLDDDDEGVPSSALREICLLKELKH
KNIVRLHDVLHSDKKLTLVFEFCDQDLKKYFDSCNGDLDPEIVKSFLFQLLKGLGFCHSR
NVLHRDLKPQNLLINRNGELKLADFGLARAFGIPVRCYSAEVVTLWYRPPDVLFGAKLYS
TSIDMWSAGCIFAELANAGRPLFPGNDVDDQLKRIFRLLGTPTEEQWPSMTKLPDYKPYP
MYPATTSLVNVVPKLNATGRDLLQNLLKCNPVQRISAEEALQHPYFSDFCPP
Drugs and Mode of Action
Drug(s) Olomoucine Drug Info Terminated Discovery agent [546498]
Inhibitor 1-phenyl-3-(2-(pyridin-4-yl)thiazol-4-yl)urea Drug Info [528986]
3-(2-phenylthiazol-4-yl)quinolin-2(1H)-one Drug Info [528992]
6-PHENYL[5H]PYRROLO[2,3-B]PYRAZINE Drug Info [551374]
9-Nitropaullone Drug Info [535564]
aloisine A Drug Info [526504]
aminopurvalanol A Drug Info [529213]
AZAKENPAULLONE Drug Info [526916]
Hymenialdisine Drug Info [535564]
Indirubin-3'-monoxime Drug Info [535564]
Indirubin-5-sulfonate Drug Info [535564]
KENPAULLONE Drug Info [526916]
MANZAMINE A Drug Info [528991]
NU6140 Drug Info [527749]
Olomoucine Drug Info [535564]
Oxindole 16 (compound 3) Drug Info [535564]
Oxindole 95 Drug Info [535564]
Purvalanol B Drug Info [535564]
Quinoxaline1 Drug Info [529213]
SU9516 Drug Info [535564]
Thieno analogue of kenpaullone Drug Info [526916]
Pathways
KEGG Pathway Axon guidance
Alzheimer&#039
s disease
Cocaine addiction
NetPath Pathway EGFR1 Signaling Pathway
TCR Signaling Pathway
PANTHER Pathway Axon guidance mediated by semaphorins
Pathway Interaction Database Reelin signaling pathway
Glucocorticoid receptor regulatory network
Lissencephaly gene (LIS1) in neuronal migration and development
EPHA forward signaling
Trk receptor signaling mediated by the MAPK pathway
Reactome DARPP-32 events
CRMPs in Sema3A signaling
Factors involved in megakaryocyte development and platelet production
WikiPathways DNA Damage Response
BDNF signaling pathway
Alzheimers Disease
Opioid Signalling
Semaphorin interactions
Factors involved in megakaryocyte development and platelet production
Nicotine Activity on Dopaminergic Neurons
miRNA Regulation of DNA Damage Response
References
Ref 546498Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008577)
Ref 526504J Med Chem. 2003 Jan 16;46(2):222-36.Aloisines, a new family of CDK/GSK-3 inhibitors. SAR study, crystal structure in complex with CDK2, enzyme selectivity, and cellular effects.
Ref 526916Bioorg Med Chem Lett. 2004 Jan 19;14(2):413-6.1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta.
Ref 527749Potentiation of paclitaxel-induced apoptosis by the novel cyclin-dependent kinase inhibitor NU6140: a possible role for survivin down-regulation. Mol Cancer Ther. 2005 Sep;4(9):1328-37.
Ref 528986Bioorg Med Chem. 2007 Oct 15;15(20):6574-95. Epub 2007 Jul 25.Structure-activity relationships of 3,4-dihydro-1H-quinazolin-2-one derivatives as potential CDK5 inhibitors.
Ref 528991J Nat Prod. 2007 Sep;70(9):1397-405. Epub 2007 Aug 21.Glycogen synthase kinase-3 (GSK-3) inhibitory activity and structure-activity relationship (SAR) studies of the manzamine alkaloids. Potential for Alzheimer's disease.
Ref 528992Bioorg Med Chem Lett. 2007 Oct 1;17(19):5384-9. Epub 2007 Aug 6.Design and synthesis of quinolin-2(1H)-one derivatives as potent CDK5 inhibitors.
Ref 529213Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8. Epub 2007 Dec 11.A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases.
Ref 535564Pharmacological inhibitors of cyclin-dependent kinases. Trends Pharmacol Sci. 2002 Sep;23(9):417-25.
Ref 551374The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.

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