ArticleACS medicinal chemistry letters2018
Development of Highly Potent and Selective Steroidal Inhibitors and Degraders of CDK8.
Article in ACS medicinal chemistry letters, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 83 citations in OpenAlex.
- Discovery of CDK8/19 inhibitors as lead compounds for IL-6-dependent lymphoma enabled by the formal synthesis of cortistatin A.Science advances · 2026Article
- Cyclins and Cyclin-Dependent Kinases: Structure, Biological Functions, and Innovative Targeting Strategies in Cancer.MedComm · 2026Review
- Targeting CDKs in the RNAPII transcription cycle.Nature reviews. Drug discovery · 2026Review
- Identification and Studies of Highly Potent and Selective Heterobifunctional Galectin‑3 Degraders.ACS medicinal chemistry letters · 2026Article
- Exploiting targeted degradation of cyclins and cyclin-dependent kinases for cancer therapeutics: a review.Journal of Zhejiang University. Science. B · 2025Review
- Targeting CDKs in cancer therapy: advances in PROTACs and molecular glues.NPJ precision oncology · 2025Review
- Synthesis and Evaluation of Antitumor and Anti-Angiogenesis Activity of Pyrone- or Pyridone-Embedded Analogs of Cortistatin A.Marine drugs · 2025Article
- How many kinases are druggable? A review of our current understanding.The Biochemical journal · 2023Article
- Emerging approaches to CDK inhibitor development, a structural perspective.RSC chemical biology · 2023Article
- Computational Exploration of Anti-cancer Potential of Flavonoids against Cyclin-Dependent Kinase 8: AnACS omega · 2023Article
- Toward the Asymmetric Synthesis of Cardenolides and Related Steroidal Systems:Organic letters · 2022Article
- Chemical inhibitors of transcription-associated kinases.Current opinion in chemical biology · 2022Review
- Review
- Proteolysis-targeting chimeras (PROTACs) in cancer therapy.Molecular cancer · 2022Review
- Degraders: The Ultimate Weapon Against Amplified Driver Kinases in Cancer.Molecular pharmacology · 2022Review
- The Renaissance of Cyclin Dependent Kinase Inhibitors.Cancers · 2022Review
- Inhibitors, PROTACs and Molecular Glues as Diverse Therapeutic Modalities to Target Cyclin-Dependent Kinase.Cancers · 2021Review
- Inhibitors of Cyclin-Dependent Kinases: Types and Their Mechanism of Action.International journal of molecular sciences · 2021Review
- Development of CDK4/6 Inhibitors: A Five Years Update.Molecules (Basel, Switzerland) · 2021Review
- Targeting Protein Kinases Degradation by PROTACs.Frontiers in chemistry · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cortistatin A is a natural product isolated from the marine sponge Corticium simplex and was found to be a potent and selective inhibitor of CDK8. Many synthetic groups have reported total syntheses of Cortistatin A; however, these syntheses require between 16 and 30 steps and report between 0.012-2% overall yields, which is not amenable to large-scale production. Owing to similarities between the complex core of Cortistatin A and the simple steroid core, we initiated a campaign to design simple, more easily prepared CDK8 inhibitors based on a steroid scaffold that would be more convenient for large-scale synthesis. Herein, we report the discovery and optimization of JH-VIII-49, a potent and selective inhibitor of CDK8 with a simple steroid core that has an eight-step synthesis with a 33% overall yield, making it suitable for large-scale preparation. Using this scaffold, we then developed a bivalent small molecule degrader, JH-XI-10-02, that can recruit the E3 ligase CRL4
Identifiers
What OpenQuestion holds
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.