Discovery and chemical biology of CDK8 inhibitors reveals insights for kinase inhibitor development

No abstract is available for this paper.

• Publication year

  2025

• Venue

  bioRxiv

• Publication date

  2025-11-07

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1101/2025.11.06.686927
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

• Phenotype-Led Identification of IL-10 Upregulators in Human CD4+ T-cells and Elucidation of Their Pharmacology as Highly Selective CDK8/CDK19 Inhibitors.

  2025cited by this paper
• Knockout of cyclin-dependent kinases 8 and 19 leads to depletion of cyclin C and suppresses spermatogenesis and male fertility in mice

  2025cited by this paper
• Mediator kinase inhibitors suppress triple-negative breast cancer growth and extend tumor suppression by mTOR and AKT inhibitors

  2024cited by this paper
• Structural basis of the human transcriptional Mediator regulated by its dissociable kinase module.

  2024cited by this paper
• Lorlatinib Versus Crizotinib in Patients With Advanced ALK-Positive Non–Small Cell Lung Cancer: 5-Year Outcomes From the Phase III CROWN Study

  2024cited by this paper
• The present and future of the Cancer Dependency Map

  2024cited by this paper
• Mediator kinase inhibition suppresses hyperactive interferon signaling in Down syndrome

  2023cited by this paper
• CDK8 and CDK19: positive regulators of signal-induced transcription and negative regulators of Mediator complex proteins

  2023cited by this paper
• Explaining Redundancy in CDK-Mediated Control of the Cell Cycle: Unifying the Continuum and Quantitative Models

  2022cited by this paper
• CDK8 and CDK19 act redundantly to control the CFTR pathway in the intestinal epithelium

  2022influential reference
• Targeting CDK4 and CDK6 in cancer

  2022cited by this paper
• Trends in kinase drug discovery: targets, indications and inhibitor design

  2021cited by this paper
• Challenges for assessing replicability in preclinical cancer biology

  2021cited by this paper
• Development of Highly Potent and Selective Pyrazolopyridine Inhibitor of CDK8/19.

  2021cited by this paper
• Investigating the replicability of preclinical cancer biology

  2021cited by this paper
• Potent and orally bioavailable CDK8 inhibitors: Design, synthesis, structure-activity relationship analysis and biological evaluation.

  2021cited by this paper
• The Cdk8 kinase module regulates interaction of the mediator complex with RNA polymerase II

  2021cited by this paper
• Selective and Potent CDK8/19 Inhibitors Enhance NK-Cell Activity and Promote Tumor Surveillance

  2020cited by this paper
• Global hyperactivation of enhancers stabilizes human and mouse naive pluripotency through inhibition of CDK8/19 Mediator kinases

  2020cited by this paper
• Cdk8 is required for establishment of H3K27me3 and gene repression by Xist and mouse development

  2020cited by this paper
• Cyclin‐dependent kinase 8/19 inhibition suppresses osteoclastogenesis by downregulating RANK and promotes osteoblast mineralization and cancellous bone healing

  2019cited by this paper
• A kinase-independent role for CDK8 in BCR-ABL1+ leukemia

  2019cited by this paper
• Systemic Toxicity Reported for CDK8/19 Inhibitors CCT251921 and MSC2530818 Is Not Due to Target Inhibition

  2019influential reference
• The Cdk8/19-cyclin C transcription regulator functions in genome replication through metazoan Sld7

  2019cited by this paper
• A Pliable Mediator Acts as a Functional Rather Than an Architectural Bridge between Promoters and Enhancers.

  2019cited by this paper
• Discovery of CDK8/CycC Ligands with a New Virtual Screening Tool

  2018cited by this paper
• In Search of Novel CDK8 Inhibitors by Virtual Screening

  2017cited by this paper
• SEL120-34A is a novel CDK8 inhibitor active in AML cells with high levels of serine phosphorylation of STAT1 and STAT5 transactivation domains

  2017cited by this paper
• Small-molecule studies identify CDK8 as a regulator of IL-10 in myeloid cells.

  2017cited by this paper
• Discovery of potent and selective CDK8 inhibitors through FBDD approach.

  2017cited by this paper
• Discovery of novel CDK8 inhibitors using multiple crystal structures in docking-based virtual screening.

  2017cited by this paper
• Studies of CDK 8/19 inhibitors: Discovery of novel and selective CDK8/19 dual inhibitors and elimination of their CYP3A4 time-dependent inhibition potential.

  2017cited by this paper
• Design and Development of a Series of Potent and Selective Type II Inhibitors of CDK8.

  2016cited by this paper
• Development of a Potent, Specific CDK8 Kinase Inhibitor Which Phenocopies CDK8/19 Knockout Cells.

  2016cited by this paper
• Discovery of Potent, Selective, and Orally Bioavailable Small-Molecule Modulators of the Mediator Complex-Associated Kinases CDK8 and CDK19

  2016cited by this paper
• Assessing the mechanism and therapeutic potential of modulators of the human Mediator complex-associated protein kinases

  2016cited by this paper
• Discovery of potent and selective CDK8 inhibitors from an HSP90 pharmacophore.

  2016cited by this paper
• A selective chemical probe for exploring the role of CDK8 and CDK19 in human disease

  2015cited by this paper
• Discovery of Potent, Orally Bioavailable, Small-Molecule Inhibitors of WNT Signaling from a Cell-Based Pathway Screen

  2015cited by this paper
• Mediator Kinase Inhibition Further Activates Super-Enhancer Associated Genes in AML

  2015cited by this paper
• Cdk8 deletion in the ApcMin murine tumour model represses EZH2 activity and accelerates tumourigenesis

  2015cited by this paper
• Improved vectors and genome-wide libraries for CRISPR screening

  2014cited by this paper
• Multiplexing Spheroid Volume, Resazurin and Acid Phosphatase Viability Assays for High-Throughput Screening of Tumour Spheroids and Stem Cell Neurospheres

  2014cited by this paper
• CDK8 Kinase Phosphorylates Transcription Factor STAT1 to Selectively Regulate the Interferon Response

  2013cited by this paper
• Monitoring Drug Target Engagement in Cells and Tissues Using the Cellular Thermal Shift Assay

  2013influential reference
• CDK8-Mediated STAT1-S727 Phosphorylation Restrains NK Cell Cytotoxicity and Tumor Surveillance

  2013cited by this paper
• HIF1A employs CDK8-mediator to stimulate RNAPII elongation in response to hypoxia.

  2013cited by this paper
• Discovery and structure-activity relationship of thienopyridine derivatives as bone anabolic agents.

  2013cited by this paper
• An integrated chemical biology approach provides insight into Cdk2 functional redundancy and inhibitor sensitivity.

  2012cited by this paper
• CDK8 maintains tumor dedifferentiation and embryonic stem cell pluripotency.

  2012cited by this paper
• The structure of CDK8/CycC implicates specificity in the CDK/cyclin family and reveals interaction with a deep pocket binder.

  2011influential reference
• CDK8 is a positive regulator of transcriptional elongation within the serum response network

  2010cited by this paper
• The histone variant macroH2A suppresses melanoma progression through regulation of CDK8

  2010cited by this paper
• CDK8 is a colorectal cancer oncogene that regulates β-catenin activity

  2008cited by this paper
• Distinct roles for Mediator Cdk8 module subunits in Drosophila development

  2007cited by this paper
• Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes.

  2006cited by this paper
• ZINC - A Free Database of Commercially Available Compounds for Virtual Screening

  2005influential reference
• Docking and scoring in virtual screening for drug discovery: methods and applications

  2004influential reference
• Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy.

  2004influential reference
• Cyclin C/CDK8 and cyclin H/CDK7/p36 are biochemically distinct CTD kinases

  1999cited by this paper
• Cyclin-dependent protein kinase and cyclin homologs SSN3 and SSN8 contribute to transcriptional control in yeast.

  1995cited by this paper
• QUANTITATIVE STUDIES OF THE GROWTH OF MOUSE EMBRYO CELLS IN CULTURE AND THEIR DEVELOPMENT INTO ESTABLISHED LINES

  1963cited by this paper
• Genome-wide identification and analysis of prognostic features in human cancers

  year unknowncited by this paper

• No citing papers are available for this paper.