Page last updated: 2024-08-07 23:33:12
Cyclin-dependent kinase 8
A cyclin-dependent kinase 8 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P49336]
Synonyms
EC 2.7.11.22;
EC 2.7.11.23;
Cell division protein kinase 8;
Mediator complex subunit CDK8;
Mediator of RNA polymerase II transcription subunit CDK8;
Protein kinase K35
Research
Bioassay Publications (23)
Timeframe | Studies on this Protein(%) | All Drugs % |
pre-1990 | 0 (0.00) | 18.7374 |
1990's | 0 (0.00) | 18.2507 |
2000's | 2 (8.70) | 29.6817 |
2010's | 13 (56.52) | 24.3611 |
2020's | 8 (34.78) | 2.80 |
Compounds (87)
Drugs with Inhibition Measurements
Drugs with Activation Measurements
Drugs with Other Measurements
Drug | Taxonomy | Measurement | Average (mM) | Bioassay(s) | Publication(s) |
cyc 202 | Homo sapiens (human) | INH | 24.5000 | 1 | 1 |
olomoucine ii | Homo sapiens (human) | INH | 11.4000 | 1 | 1 |
Discovery of 3-Benzyl-1-( trans-4-((5-cyanopyridin-2-yl)amino)cyclohexyl)-1-arylurea Derivatives as Novel and Selective Cyclin-Dependent Kinase 12 (CDK12) Inhibitors.Journal of medicinal chemistry, , 09-13, Volume: 61, Issue:17, 2018
Discovery of novel CDK8 inhibitors using multiple crystal structures in docking-based virtual screening.European journal of medicinal chemistry, , Mar-31, Volume: 129, 2017
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
A quantitative analysis of kinase inhibitor selectivity.Nature biotechnology, , Volume: 26, Issue:1, 2008
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).Blood, , Oct-01, Volume: 114, Issue:14, 2009
A Selective and Brain Penetrant p38αMAPK Inhibitor Candidate for Neurologic and Neuropsychiatric Disorders That Attenuates Neuroinflammation and Cognitive Dysfunction.Journal of medicinal chemistry, , 06-13, Volume: 62, Issue:11, 2019
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
A quantitative analysis of kinase inhibitor selectivity.Nature biotechnology, , Volume: 26, Issue:1, 2008
From Structure Modification to Drug Launch: A Systematic Review of the Ongoing Development of Cyclin-Dependent Kinase Inhibitors for Multiple Cancer Therapy.Journal of medicinal chemistry, , 05-12, Volume: 65, Issue:9, 2022
Synthesis and in vitro biological evaluation of 2,6,9-trisubstituted purines targeting multiple cyclin-dependent kinases.European journal of medicinal chemistry, , Volume: 61, 2013
A quantitative analysis of kinase inhibitor selectivity.Nature biotechnology, , Volume: 26, Issue:1, 2008
[no title available]Journal of medicinal chemistry, , 09-22, Volume: 65, Issue:18, 2022
[no title available]Journal of medicinal chemistry, , 10-13, Volume: 65, Issue:19, 2022
Identification of 3, 4-disubstituted pyridine derivatives as novel CDK8 inhibitors.European journal of medicinal chemistry, , Nov-05, Volume: 223, 2021
Pyrido[2,3-b][1,5]benzoxazepin-5(6H)-one derivatives as CDK8 inhibitors.European journal of medicinal chemistry, , Sep-01, Volume: 201, 2020
CDK8 as a therapeutic target for cancers and recent developments in discovery of CDK8 inhibitors.European journal of medicinal chemistry, , Feb-15, Volume: 164, 2019
Cyclin-Dependent Kinase 8: A New Hope in Targeted Cancer Therapy?Journal of medicinal chemistry, , 06-28, Volume: 61, Issue:12, 2018
Design and Development of a Series of Potent and Selective Type II Inhibitors of CDK8.ACS medicinal chemistry letters, , Jun-09, Volume: 7, Issue:6, 2016
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).Blood, , Oct-01, Volume: 114, Issue:14, 2009
A quantitative analysis of kinase inhibitor selectivity.Nature biotechnology, , Volume: 26, Issue:1, 2008
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).Blood, , Oct-01, Volume: 114, Issue:14, 2009
A quantitative analysis of kinase inhibitor selectivity.Nature biotechnology, , Volume: 26, Issue:1, 2008
Lessons Learned from Past Cyclin-Dependent Kinase Drug Discovery Efforts.Journal of medicinal chemistry, , 05-12, Volume: 65, Issue:9, 2022
Discovery and Anti-Inflammatory Activity Evaluation of a Novel CDK8 Inhibitor through Upregulation of IL-10 for the Treatment of Inflammatory Bowel Disease Journal of medicinal chemistry, , 05-26, Volume: 65, Issue:10, 2022
CDK8 as a therapeutic target for cancers and recent developments in discovery of CDK8 inhibitors.European journal of medicinal chemistry, , Feb-15, Volume: 164, 2019
Cyclin-Dependent Kinase 8: A New Hope in Targeted Cancer Therapy?Journal of medicinal chemistry, , 06-28, Volume: 61, Issue:12, 2018
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).Blood, , Oct-01, Volume: 114, Issue:14, 2009
A quantitative analysis of kinase inhibitor selectivity.Nature biotechnology, , Volume: 26, Issue:1, 2008
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).Blood, , Oct-01, Volume: 114, Issue:14, 2009
A quantitative analysis of kinase inhibitor selectivity.Nature biotechnology, , Volume: 26, Issue:1, 2008
Cyclin-Dependent Kinase 8: A New Hope in Targeted Cancer Therapy?Journal of medicinal chemistry, , 06-28, Volume: 61, Issue:12, 2018
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
A quantitative analysis of kinase inhibitor selectivity.Nature biotechnology, , Volume: 26, Issue:1, 2008
CDK8 as a therapeutic target for cancers and recent developments in discovery of CDK8 inhibitors.European journal of medicinal chemistry, , Feb-15, Volume: 164, 2019
Cyclin-Dependent Kinase 8: A New Hope in Targeted Cancer Therapy?Journal of medicinal chemistry, , 06-28, Volume: 61, Issue:12, 2018
Design and synthesis of selective CDK8/19 dual inhibitors: Discovery of 4,5-dihydrothieno[3',4':3,4]benzo[1,2-d]isothiazole derivatives.Bioorganic & medicinal chemistry, , 04-15, Volume: 25, Issue:8, 2017
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).Blood, , Oct-01, Volume: 114, Issue:14, 2009
[no title available]Journal of medicinal chemistry, , 10-13, Volume: 65, Issue:19, 2022
Potent and orally bioavailable CDK8 inhibitors: Design, synthesis, structure-activity relationship analysis and biological evaluation.European journal of medicinal chemistry, , Mar-15, Volume: 214, 2021
Discovery of Potent, Selective, and Orally Bioavailable Small-Molecule Modulators of the Mediator Complex-Associated Kinases CDK8 and CDK19.Journal of medicinal chemistry, , Feb-11, Volume: 59, Issue:3, 2016
Enables
This protein enables 8 target(s):
Target | Category | Definition |
protein kinase activity | molecular function | Catalysis of the phosphorylation of an amino acid residue in a protein, usually according to the reaction: a protein + ATP = a phosphoprotein + ADP. [PMID:25399640] |
cyclin-dependent protein serine/threonine kinase activity | molecular function | Cyclin-dependent catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate. [GOC:pr, GOC:rn, PMID:7877684, PMID:9841670] |
protein binding | molecular function | Binding to a protein. [GOC:go_curators] |
ATP binding | molecular function | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. [ISBN:0198506732] |
RNA polymerase II CTD heptapeptide repeat kinase activity | molecular function | Catalysis of the reaction: ATP + RNA polymerase II large subunit CTD heptapeptide repeat (consensus YSPTSPS) = ADP + H+ + phosphorylated RNA polymerase II. [EC:2.7.11.23, GOC:mah, PMID:28248323] |
ubiquitin protein ligase activity | molecular function | Catalysis of the transfer of ubiquitin to a substrate protein via the reaction X-ubiquitin + S = X + S-ubiquitin, where X is either an E2 or E3 enzyme, the X-ubiquitin linkage is a thioester bond, and the S-ubiquitin linkage is an amide bond: an isopeptide bond between the C-terminal glycine of ubiquitin and the epsilon-amino group of lysine residues in the substrate or, in the linear extension of ubiquitin chains, a peptide bond the between the C-terminal glycine and N-terminal methionine of ubiquitin residues. [GOC:BioGRID, GOC:dph, GOC:mah, GOC:tb, PMID:22863777] |
protein serine kinase activity | molecular function | Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate. [RHEA:17989] |
protein serine/threonine kinase activity | molecular function | Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate. [GOC:bf, MetaCyc:PROTEIN-KINASE-RXN, PMID:2956925] |
Located In
This protein is located in 3 target(s):
Target | Category | Definition |
nucleus | cellular component | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. [GOC:go_curators] |
nucleoplasm | cellular component | That part of the nuclear content other than the chromosomes or the nucleolus. [GOC:ma, ISBN:0124325653] |
nucleolus | cellular component | A small, dense body one or more of which are present in the nucleus of eukaryotic cells. It is rich in RNA and protein, is not bounded by a limiting membrane, and is not seen during mitosis. Its prime function is the transcription of the nucleolar DNA into 45S ribosomal-precursor RNA, the processing of this RNA into 5.8S, 18S, and 28S components of ribosomal RNA, and the association of these components with 5S RNA and proteins synthesized outside the nucleolus. This association results in the formation of ribonucleoprotein precursors; these pass into the cytoplasm and mature into the 40S and 60S subunits of the ribosome. [ISBN:0198506732] |
Active In
This protein is active in 1 target(s):
Target | Category | Definition |
nucleus | cellular component | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. [GOC:go_curators] |
Part Of
This protein is part of 5 target(s):
Target | Category | Definition |
cyclin-dependent protein kinase holoenzyme complex | cellular component | Cyclin-dependent protein kinases (CDKs) are enzyme complexes that contain a kinase catalytic subunit associated with a regulatory cyclin partner. [GOC:krc, PMID:11602261] |
CKM complex | cellular component | Cyclin-dependent kinase complex which reversibly associates with the Mediator complex. In Saccharomyces cerevisiae it consists of SSN2, SSN3, SSN8 and SRB8. [GOC:bhm, PMID:12200444] |
ubiquitin ligase complex | cellular component | A protein complex that includes a ubiquitin-protein ligase and enables ubiquitin protein ligase activity. The complex also contains other proteins that may confer substrate specificity on the complex. [GOC:jh2, PMID:9529603] |
mediator complex | cellular component | A protein complex that interacts with the carboxy-terminal domain of the largest subunit of RNA polymerase II and plays an active role in transducing the signal from a transcription factor to the transcriptional machinery. The mediator complex is required for activation of transcription of most protein-coding genes, but can also act as a transcriptional corepressor. The Saccharomyces complex contains several identifiable subcomplexes: a head domain comprising Srb2, -4, and -5, Med6, -8, and -11, and Rox3 proteins; a middle domain comprising Med1, -4, and -7, Nut1 and -2, Cse2, Rgr1, Soh1, and Srb7 proteins; a tail consisting of Gal11p, Med2p, Pgd1p, and Sin4p; and a regulatory subcomplex comprising Ssn2, -3, and -8, and Srb8 proteins. Metazoan mediator complexes have similar modular structures and include homologs of yeast Srb and Med proteins. [PMID:11454195, PMID:16168358, PMID:17870225] |
protein-containing complex | cellular component | A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together. [GOC:dos, GOC:mah] |
Involved In
This protein is involved in 5 target(s):
Target | Category | Definition |
protein ubiquitination | biological process | The process in which one or more ubiquitin groups are added to a protein. [GOC:ai] |
positive regulation of transcription by RNA polymerase II | biological process | Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter. [GOC:go_curators, GOC:txnOH] |
regulation of cell cycle | biological process | Any process that modulates the rate or extent of progression through the cell cycle. [GOC:ai, GOC:dph, GOC:tb] |
negative regulation of triglyceride metabolic process | biological process | Any process that decreases the frequency, rate or extent of the chemical reactions and pathways involving triglyceride, any triester of glycerol. [GOC:dph, GOC:sl, GOC:tb] |
protein phosphorylation | biological process | The process of introducing a phosphate group on to a protein. [GOC:hb] |