Target Information
Target General Infomation | |||||
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Target ID |
T89361
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Former ID |
TTDC00169
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Target Name |
Cell division protein kinase 6
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Gene Name |
CDK6
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Synonyms |
Cyclin-dependent kinase 6; Serine/threonine protein kinase PLSTIRE; Serine/threonine-protein kinase PLSTIRE; CDK6
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Target Type |
Successful
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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.
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BioChemical Class |
Kinase
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Target Validation |
T89361
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UniProt ID | |||||
EC Number |
EC 2.7.11.22
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Sequence |
MEKDGLCRADQQYECVAEIGEGAYGKVFKARDLKNGGRFVALKRVRVQTGEEGMPLSTIR
EVAVLRHLETFEHPNVVRLFDVCTVSRTDRETKLTLVFEHVDQDLTTYLDKVPEPGVPTE TIKDMMFQLLRGLDFLHSHRVVHRDLKPQNILVTSSGQIKLADFGLARIYSFQMALTSVV VTLWYRAPEVLLQSSYATPVDLWSVGCIFAEMFRRKPLFRGSSDVDQLGKILDVIGLPGE EDWPRDVALPRQAFHSKSAQPIEKFVTDIDELGKDLLLKCLTFNPAKRISAYSALSHPYF QDLERCKENLDSHLPPSQNTSELNTA |
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Structure |
1BI7; 1BI8; 1BLX; 1G3N; 1JOW; 1XO2; 2EUF; 2F2C; 3NUP; 3NUX; 4AUA; 4EZ5; 4TTH
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Drugs and Mode of Action | |||||
Drug(s) | Ribociclib Succinate | Drug Info | Approved | Hormone receptor-positive and HER2-negative advanced or metastatic breast cancer | [1] |
LEE011 | Drug Info | Phase 3 | Cancer | [2], [3] | |
LY2835219 | Drug Info | Phase 3 | Cancer | [4], [5] | |
PD-332991 | Drug Info | Phase 2 | Cancer | [6] | |
G1T28-1 | Drug Info | Phase 1 | Cancer | [7] | |
INOC-005 | Drug Info | Preclinical | Cancer | [8] | |
Capridine-beta | Drug Info | Discontinued in Phase 4 | Psoriasis | [9] | |
CYC-103 | Drug Info | Terminated | Cancer | [10] | |
Inhibitor | 3,4-di-(4-methoxyphenyl)-1H-pyrrole-2,5-dione | Drug Info | [11] | ||
3,4-diphenyl-1H-pyrrole-2,5-dione | Drug Info | [11] | |||
3,7,3',4'-TETRAHYDROXYFLAVONE | Drug Info | [12] | |||
3-(4-methoxyphenyl)-4-phenyl-1H-pyrrole-2,5-dione | Drug Info | [11] | |||
APIGENIN | Drug Info | [13] | |||
Capridine-beta | Drug Info | [14] | |||
CHRYSIN | Drug Info | [13] | |||
CYC-103 | Drug Info | [15] | |||
Deschloroflavopiridol | Drug Info | [16] | |||
Fascaplysin | Drug Info | [16] | |||
FISETIN | Drug Info | [13] | |||
INOC-005 | Drug Info | [17] | |||
PD0183813 | Drug Info | [16] | |||
RGB-286147 | Drug Info | [18] | |||
Modulator | G1T28-1 | Drug Info | [19] | ||
LEE011 | Drug Info | [20] | |||
LY2835219 | Drug Info | [19] | |||
PD-332991 | Drug Info | ||||
Ribociclib Succinate | Drug Info | [21] | |||
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 1 | Drugs@FDA (Edaravone) | ||||
REF 2 | ClinicalTrials.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 3 | (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 4 | ClinicalTrials.gov (NCT02152631) A Study of Abemaciclib (LY2835219) in Participants With Previously Treated Lung Cancer. U.S. National Institutes of Health. | ||||
REF 5 | (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 6 | ClinicalTrials.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 7 | ClinicalTrials.gov (NCT02243150) Safety, Pharmacokinetic and Pharmacodynamic Study of the CDK 4/6 Inhibitor G1T28-1. U.S. National Institutes of Health. | ||||
REF 8 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022337) | ||||
REF 9 | 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81. | ||||
REF 10 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015455) | ||||
REF 11 | J Med Chem. 2006 Feb 23;49(4):1271-81.Design, synthesis, and biological evaluation of 3,4-diarylmaleimides as angiogenesis inhibitors. | ||||
REF 12 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | ||||
REF 13 | J 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 14 | Agreement signed with Prostagenics to develop prostate cancer treatment. Innovate Oncology, Inc. 2005. | ||||
REF 15 | WO patent application no. 2007,0898,78, Sutures and anti-scarring agents. | ||||
REF 16 | Pharmacological inhibitors of cyclin-dependent kinases. Trends Pharmacol Sci. 2002 Sep;23(9):417-25. | ||||
REF 17 | What are next generation innovative therapeutic targets. J Pharmacol Exp Ther. 2009 Jul;330(1):304-15. | ||||
REF 18 | Proc 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 19 | Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41. | ||||
REF 20 | Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma. Clin Cancer Res. 2013 Nov 15;19(22):6173-82. | ||||
REF 21 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. |
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