ArticleNature chemical biology2015
A selective chemical probe for exploring the role of CDK8 and CDK19 in human disease.
Article in Nature chemical biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
79 citing papers in PubMed, 143 citations in OpenAlex.
- Targeting CDKs in the RNAPII transcription cycle.Nature reviews. Drug discovery · 2026Review
- The Role of Transcriptional and Atypical Cyclin-Dependent Protein Kinases in Melanoma.Cancers · 2026Review
- A novel CDK8/19 inhibitor RO8323 mitigates allograft rejection through dual mechanisms of action to modulate regulatory T cell and myeloid cell.Acta pharmacologica Sinica · 2026Article
- Vitamin D3 ameliorates R-loop-induced replication stress and chromosomal instability in MED12-mutant uterine fibroids.Scientific reports · 2026Article
- Loss of the tumor suppressor PTEN activates cell-intrinsic interferon signaling to drive immune resistance.Genes & development · 2026Article
- Structural basis of the cyclin Y/14-3-3 protein-mediated activation of CDK16.Nature communications · 2026Article
- Human DEAH-box helicase 8 regulates HSF1-mediated stress response and cancer-associated pre-mRNA splicing in tumour cells.NAR cancer · 2026Article
- Vitamin D3 ameliorates R-loop-induced replication stress and chromosomal instability in MED12-mutant uterine fibroids.Research square · 2026Article
- Expanding Therapeutic Horizons with Indazole-Based Compounds: A Review of Anticancer, Antimicrobial, and Neuroprotective Applications.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2026Review
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- Dual Modes of Gene Regulation by CDK12.bioRxiv : the preprint server for biology · 2025Article
- Target discovery-directed pharmacological mechanism elucidation of bioactive natural products.Medical review (2021) · 2025Review
- Mediator Kinase Inhibitor Selectivity and Activity in Colorectal Cancer.ACS chemical biology · 2025Article
- Mediator kinase inhibition drives myometrial stem cell differentiation and the uterine fibroid phenotype through super-enhancer reprogramming.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Cyclin-dependent protein kinases and cell cycle regulation in biology and disease.Signal transduction and targeted therapy · 2025Review
- Mediator kinase inhibition drives myometrial stem cell differentiation and the uterine fibroid phenotype through super-enhancer reprogramming.Research square · 2024Article
- Article
- Discovery of novel and potent CDK8 inhibitors for the treatment of acute myeloid leukaemia.Journal of enzyme inhibition and medicinal chemistry · 2024Article
- Mediator kinase inhibition impedes transcriptional plasticity and prevents resistance to ERK/MAPK-targeted therapy in KRAS-mutant cancers.NPJ precision oncology · 2024Article
- Targeting super-enhancer activity for colorectal cancer therapy.American journal of translational research · 2024Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
31 authors at 3 institutions in 2 countries.
Funding
Abstract
There is unmet need for chemical tools to explore the role of the Mediator complex in human pathologies ranging from cancer to cardiovascular disease. Here we determine that CCT251545, a small-molecule inhibitor of the WNT pathway discovered through cell-based screening, is a potent and selective chemical probe for the human Mediator complex-associated protein kinases CDK8 and CDK19 with >100-fold selectivity over 291 other kinases. X-ray crystallography demonstrates a type 1 binding mode involving insertion of the CDK8 C terminus into the ligand binding site. In contrast to type II inhibitors of CDK8 and CDK19, CCT251545 displays potent cell-based activity. We show that CCT251545 and close analogs alter WNT pathway-regulated gene expression and other on-target effects of modulating CDK8 and CDK19, including expression of genes regulated by STAT1. Consistent with this, we find that phosphorylation of STAT1(SER727) is a biomarker of CDK8 kinase activity in vitro and in vivo. Finally, we demonstrate in vivo activity of CCT251545 in WNT-dependent tumors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.