Target General Infomation
Target ID
T89361
Former ID
TTDC00169
Target Name
Cell division protein kinase 6
Gene Name
CDK6
Synonyms
Cyclin-dependent kinase 6; Serine/threonine protein kinase PLSTIRE; Serine/threonine-protein kinase PLSTIRE; CDK6
Target Type
Successful
Disease Cancer [ICD9: 140-229; ICD10: C00-C96]
Hormone receptor-positive and HER2-negative advanced or metastatic breast cancer [ICD10: C50]
Psoriasis [ICD9: 696; ICD10: L40]
Function
Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and regulates negatively cell differentiation, but is required for the proliferation of specific cell types (e.g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans.
BioChemical Class
Kinase
Target Validation
T89361
UniProt ID
EC Number
EC 2.7.11.22
Sequence
MEKDGLCRADQQYECVAEIGEGAYGKVFKARDLKNGGRFVALKRVRVQTGEEGMPLSTIR
EVAVLRHLETFEHPNVVRLFDVCTVSRTDRETKLTLVFEHVDQDLTTYLDKVPEPGVPTE
TIKDMMFQLLRGLDFLHSHRVVHRDLKPQNILVTSSGQIKLADFGLARIYSFQMALTSVV
VTLWYRAPEVLLQSSYATPVDLWSVGCIFAEMFRRKPLFRGSSDVDQLGKILDVIGLPGE
EDWPRDVALPRQAFHSKSAQPIEKFVTDIDELGKDLLLKCLTFNPAKRISAYSALSHPYF
QDLERCKENLDSHLPPSQNTSELNTA
Structure
1BI7; 1BI8; 1BLX; 1G3N; 1JOW; 1XO2; 2EUF; 2F2C; 3NUP; 3NUX; 4AUA; 4EZ5; 4TTH
Drugs and Mode of Action
Drug(s) Ribociclib Succinate Drug Info Approved Hormone receptor-positive and HER2-negative advanced or metastatic breast cancer [889446]
LEE011 Drug Info Phase 3 Cancer [524461], [542405]
LY2835219 Drug Info Phase 3 Cancer [524783], [542404]
PD-332991 Drug Info Phase 2 Cancer [524116]
G1T28-1 Drug Info Phase 1 Cancer [524917]
INOC-005 Drug Info Preclinical Cancer [548139]
Capridine-beta Drug Info Discontinued in Phase 4 Psoriasis [533123]
CYC-103 Drug Info Terminated Cancer [547357]
Inhibitor 3,4-di-(4-methoxyphenyl)-1H-pyrrole-2,5-dione Drug Info [528032]
3,4-diphenyl-1H-pyrrole-2,5-dione Drug Info [528032]
3,7,3',4'-TETRAHYDROXYFLAVONE Drug Info [551374]
3-(4-methoxyphenyl)-4-phenyl-1H-pyrrole-2,5-dione Drug Info [528032]
APIGENIN Drug Info [527422]
Capridine-beta Drug Info [551434]
CHRYSIN Drug Info [527422]
CYC-103 Drug Info [550130]
Deschloroflavopiridol Drug Info [535564]
Fascaplysin Drug Info [535564]
FISETIN Drug Info [527422]
INOC-005 Drug Info [530064]
PD0183813 Drug Info [535564]
RGB-286147 Drug Info [529213]
Modulator G1T28-1 Drug Info [1572591]
LEE011 Drug Info [532480]
LY2835219 Drug Info [1572591]
PD-332991 Drug Info
Ribociclib Succinate Drug Info [556264]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Cell cycle
p53 signaling pathway
PI3K-Akt signaling pathway
Hepatitis B
Measles
Pathways in cancer
Viral carcinogenesis
MicroRNAs in cancer
Pancreatic cancer
Glioma
Melanoma
Chronic myeloid leukemia
Small cell lung cancer
Non-small cell lung cancer
NetPath Pathway TGF_beta_Receptor Signaling Pathway
Pathway Interaction Database p73 transcription factor network
Coregulation of Androgen receptor activity
C-MYB transcription factor network
IL2 signaling events mediated by STAT5
Regulation of retinoblastoma protein
Reactome Oxidative Stress Induced Senescence
Senescence-Associated Secretory Phenotype (SASP)
Oncogene Induced Senescence
Cyclin D associated events in G1
WikiPathways DNA Damage Response
G1 to S cell cycle control
Wnt Signaling Pathway Netpath
Retinoblastoma (RB) in Cancer
Signaling Pathways in Glioblastoma
Metastatic brain tumor
miR-targeted genes in muscle cell - TarBase
miR-targeted genes in lymphocytes - TarBase
miR-targeted genes in leukocytes - TarBase
miR-targeted genes in epithelium - TarBase
Mitotic G1-G1/S phases
Cell Cycle
miRNAs involved in DNA damage response
miRNA Regulation of DNA Damage Response
References
Ref 524116ClinicalTrials.gov (NCT01723774) PD 0332991 and Anastrozole for Stage 2 or 3 Estrogen Receptor Positive and HER2 Negative Breast Cancer. U.S. National Institutes of Health.
Ref 524461ClinicalTrials.gov (NCT01958021) Study of Efficacy and Safety of LEE011 in Postmenopausal Women With Advanced Breast Cancer.(MONALEESA-2). U.S. National Institutes of Health.
Ref 524783ClinicalTrials.gov (NCT02152631) A Study of Abemaciclib (LY2835219) in Participants With Previously Treated Lung Cancer. U.S. National Institutes of Health.
Ref 524917ClinicalTrials.gov (NCT02243150) Safety, Pharmacokinetic and Pharmacodynamic Study of the CDK 4/6 Inhibitor G1T28-1. U.S. National Institutes of Health.
Ref 5331232014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
Ref 542404(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7382).
Ref 542405(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7383).
Ref 547357Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015455)
Ref 548139Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022337)
Ref 889446Drugs@FDA (Edaravone)
Ref
Ref 527422J Med Chem. 2005 Feb 10;48(3):737-43.Crystal structure of a human cyclin-dependent kinase 6 complex with a flavonol inhibitor, fisetin.
Ref 528032J Med Chem. 2006 Feb 23;49(4):1271-81.Design, synthesis, and biological evaluation of 3,4-diarylmaleimides as angiogenesis 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 530064What are next generation innovative therapeutic targets. J Pharmacol Exp Ther. 2009 Jul;330(1):304-15.
Ref 532480Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma. Clin Cancer Res. 2013 Nov 15;19(22):6173-82.
Ref 535564Pharmacological inhibitors of cyclin-dependent kinases. Trends Pharmacol Sci. 2002 Sep;23(9):417-25.
Ref 550130WO patent application no. 2007,0898,78, Sutures and anti-scarring agents.
Ref 551374The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
Ref 551434Agreement signed with Prostagenics to develop prostate cancer treatment. Innovate Oncology, Inc. 2005.
Ref 556264Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
Ref 1572591Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.

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