ArticleCell chemical biology2016
Structural Basis for KDM5A Histone Lysine Demethylase Inhibition by Diverse Compounds.
Article in Cell chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 100 citations in OpenAlex.
- Design and synthesis of novel quinazoline derivatives as KDM6B selective inhibitors.Molecular diversity · 2026Article
- l-2-Hydroxyglutarate impairs neuronal differentiation through epigenetic activation of MYC expression.The Journal of clinical investigation · 2026Article
- Exploratory study of the dysregulation of age-related changes in neural/glial antigen 2 and neuroinflammation markers in individuals with major depression.Brain, behavior, & immunity - health · 2025Article
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- Histone demethylase inhibitors: developmental insights and current status.Future medicinal chemistry · 2025Review
- Current advances and future directions in targeting histone demethylases for cancer therapy.Molecules and cells · 2025Review
- Phytochemical synergies in BK002: advanced molecular docking insights for targeted prostate cancer therapy.Frontiers in pharmacology · 2025Review
- JmjC catalysed histone H2a N-methyl arginine demethylation and C4-arginine hydroxylation reveals importance of sequence-reactivity relationships.Communications biology · 2024Article
- Histone demethylase KDM5 regulates cardiomyocyte maturation by promoting fatty acid oxidation, oxidative phosphorylation, and myofibrillar organization.Cardiovascular research · 2024Article
- Pharmacological agents targeting drug-tolerant persister cells in cancer.Pharmacological research · 2024Review
- Identifying ligands for the PHD1 finger of KDM5A through high-throughput screening.RSC chemical biology · 2024Article
- Gene Regulation and Mitochondrial Activity During White and Brown Adipogenesis Are Modulated by KDM5 Histone Demethylase.Journal of the Endocrine Society · 2024Article
- Recent developments in catalysis and inhibition of the Jumonji histone demethylases.Current opinion in structural biology · 2023Review
- KDM5 Lysine Demethylases in Pathogenesis, from Basic Science Discovery to the Clinic.Advances in experimental medicine and biology · 2023Article
- Structural analysis of the 2-oxoglutarate binding site of the circadian rhythm linked oxygenase JMJD5.Scientific reports · 2022Article
- JMJD family proteins in cancer and inflammation.Signal transduction and targeted therapy · 2022Review
- KDM5A Inhibits Antitumor Immune Responses Through Downregulation of the Antigen-Presentation Pathway in Ovarian Cancer.Cancer immunology research · 2022Article
- Targeting KDM4 for treating PAX3-FOXO1-driven alveolar rhabdomyosarcoma.Science translational medicine · 2022Article
- Male-Specific Activation of Lysine Demethylases 5B and 5C Mediates Alcohol-Induced Liver Injury and Hepatocyte Dedifferentiation.Hepatology communications · 2022Article
- Epigenetic Factors as Etiological Agents, Diagnostic Markers, and Therapeutic Targets for Luminal Breast Cancer.Biomedicines · 2022Review
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23 authors at 4 institutions in 1 country.
Funding
Abstract
The KDM5/JARID1 family of Fe(II)- and α-ketoglutarate-dependent demethylases removes methyl groups from methylated lysine 4 of histone H3. Accumulating evidence supports a role for KDM5 family members as oncogenic drivers. We compare the in vitro inhibitory properties and binding affinity of ten diverse compounds with all four family members, and present the crystal structures of the KDM5A-linked Jumonji domain in complex with eight of these inhibitors in the presence of Mn(II). All eight inhibitors structurally examined occupy the binding site of α-ketoglutarate, but differ in their specific binding interactions, including the number of ligands involved in metal coordination. We also observed inhibitor-induced conformational changes in KDM5A, particularly those residues involved in the binding of α-ketoglutarate, the anticipated peptide substrate, and intramolecular interactions. We discuss how particular chemical moieties contribute to inhibitor potency and suggest strategies that might be utilized in the successful design of selective and potent epigenetic inhibitors.
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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.