ArticleNature communications2017
Highly selective inhibition of histone demethylases by de novo macrocyclic peptides.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
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
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 146 citations in OpenAlex.
- Advances in pathogenesis of preeclampsia.Archives of gynecology and obstetrics · 2024Pooled it
- DHODH is the key target of the KDM4 inhibitor QC6352 in glioblastoma stem cells.Nature chemical biology · 2026Article
- A De Novo Peptide That Induces Axonal Growth Through TrkB Activation.Chembiochem : a European journal of chemical biology · 2026Article
- mRNA Display for Identifying Peptide Substrates of Enzymes.Biochemistry · 2026Review
- Stapled histone H3 tails are super-substrates for lysine methyltransferase SETD7.Chemical science · 2026Article
- Discovery of Supra-Bivalent GSK3β Inhibitory Peptides Containing an ATP-Mimetic Amino Acid.Journal of the American Chemical Society · 2026Article
- mRNA display-enabled discovery of proximity-triggered covalent peptide-drug conjugates.Acta pharmaceutica Sinica. B · 2025Article
- A general assay platform to study protein pharmacology using ligand-dependent structural dynamics.Nature communications · 2025Article
- Genetic Code Expansion: Recent Developments and Emerging Applications.Chemical reviews · 2025Review
- JmjC catalysed histone H2a N-methyl arginine demethylation and C4-arginine hydroxylation reveals importance of sequence-reactivity relationships.Communications biology · 2024Article
- Tackling Undruggable Targets with Designer Peptidomimetics and Synthetic Biologics.Chemical reviews · 2024Review
- Selection of Nucleotide-Encoded Mass Libraries of Macrocyclic Peptides for Inaccessible Drug Targets.Chemical reviews · 2024Review
- Encoding and display technologies for combinatorial libraries in drug discovery: The coming of age from biology to therapy.Acta pharmaceutica Sinica. B · 2024Review
- mRNA Display Pipeline for Protein Biosensor Construction.ACS sensors · 2024Article
- The emerging roles of lysine-specific demethylase 4A in cancer: Implications in tumorigenesis and therapeutic opportunities.Genes & diseases · 2024Review
- Macrocyclic Peptides Closed by a Thioether-Bipyridyl Unit That Grants Cell Membrane Permeability.ACS bio & med chem Au · 2023Article
- Identification of Covalent Cyclic Peptide Inhibitors in mRNA Display.Journal of the American Chemical Society · 2023Article
- Cyclic peptides target the aromatic cage of a PHD-finger reader domain to modulate epigenetic protein function.Chemical science · 2023Article
- In vitro selection of macrocyclic peptide inhibitors containing cyclic γNature chemistry · 2023Article
- Development of a Cyclic, Cell Penetrating Peptide Compatible with In Vitro Selection Strategies.ACS chemical biology · 2023Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
Abstract
The JmjC histone demethylases (KDMs) are linked to tumour cell proliferation and are current cancer targets; however, very few highly selective inhibitors for these are available. Here we report cyclic peptide inhibitors of the KDM4A-C with selectivity over other KDMs/2OG oxygenases, including closely related KDM4D/E isoforms. Crystal structures and biochemical analyses of one of the inhibitors (CP2) with KDM4A reveals that CP2 binds differently to, but competes with, histone substrates in the active site. Substitution of the active site binding arginine of CP2 to N-ɛ-trimethyl-lysine or methylated arginine results in cyclic peptide substrates, indicating that KDM4s may act on non-histone substrates. Targeted modifications to CP2 based on crystallographic and mass spectrometry analyses results in variants with greater proteolytic robustness. Peptide dosing in cells manifests KDM4A target stabilization. Although further development is required to optimize cellular activity, the results reveal the feasibility of highly selective non-metal chelating, substrate-competitive inhibitors of the JmjC KDMs.
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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.