ArticleJournal of medicinal chemistry2014
KDM4B as a target for prostate cancer: structural analysis and selective inhibition by a novel inhibitor.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
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Who cites it
58 citing papers in PubMed, 104 citations in OpenAlex.
- The JMJD family histone demethylases: structure, mechanism of action, diseases and therapeutic targets.Molecular biomedicine · 2026Review
- KDM4A promotes NEPC progression through regulation of MYC expression.Cancer letters · 2026Article
- Histone lysine demethylases in breast cancer: molecular mechanisms, biological functions, and therapeutic intervention.Molecular cancer · 2025Review
- Anti-tumor activity of CDYL2b in prostate cancer.Cancer letters · 2025Article
- KDM4A-driven SMAD5/TGFβ axis activation as a therapeutic target in cholangiocarcinoma: mechanistic insights and translational implications.Cell & bioscience · 2025Article
- Histone demethylase inhibitors: developmental insights and current status.Future medicinal chemistry · 2025Review
- Epigenetic Dysregulation in Cancer: Implications for Gene Expression and DNA Repair-Associated Pathways.International journal of molecular sciences · 2025Review
- KDM4C works in concert with GATA1 to regulate heme metabolism in head and neck squamous cell carcinoma.Cellular and molecular life sciences : CMLS · 2025Article
- Targeting N-Methyl-lysine Histone Demethylase KDM4 in Cancer: Natural Products Inhibitors as a Driving Force for Epigenetic Drug Discovery.ChemMedChem · 2025Review
- Lysine and arginine methylation of transcription factors.Cellular and molecular life sciences : CMLS · 2024Review
- Hypoxic Memory Mediates Prolonged Tumor-Intrinsic Type I Interferon Suppression to Promote Breast Cancer Progression.Cancer research · 2024Article
- The emerging roles of lysine-specific demethylase 4A in cancer: Implications in tumorigenesis and therapeutic opportunities.Genes & diseases · 2024Review
- Vitamin BNature metabolism · 2023Article
- Intrinsic catalytic properties of histone H3 lysine-9 methyltransferases preserve monomethylation levels under low S-adenosylmethionine.The Journal of biological chemistry · 2023Article
- Epigenetic (De)regulation in Prostate Cancer.Cancer treatment and research · 2023Article
- Methylation of the JMJD2B epigenetic regulator differentially affects its ability to coactivate the ETV1 and JUN transcription factors.International journal of biochemistry and molecular biology · 2023Article
- KDM4 Demethylases: Structure, Function, and Inhibitors.Advances in experimental medicine and biology · 2023Article
- JMJD8 Functions as a Novel AKT1 Lysine Demethylase.International journal of molecular sciences · 2022Article
- Differential enrichment of H3K9me3 in intrahepatic cholangiocarcinoma.BMC medical genomics · 2022Article
- Interaction of huntingtin with PRMTs and its subsequent arginine methylation affects HTT solubility, phase transition behavior and neuronal toxicity.Human molecular genetics · 2022Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
The KDM4/JMJD2 Jumonji C-containing histone lysine demethylases (KDM4A-KDM4D), which selectively remove the methyl group(s) from tri/dimethylated lysine 9/36 of H3, modulate transcriptional activation and genome stability. The overexpression of KDM4A/KDM4B in prostate cancer and their association with androgen receptor suggest that KDM4A/KDM4B are potential progression factors for prostate cancer. Here, we report the crystal structure of the KDM4B·pyridine 2,4-dicarboxylic acid·H3K9me3 ternary complex, revealing the core active-site region and a selective K9/K36 site. A selective KDM4A/KDM4B inhibitor, 4, that occupies three subsites in the binding pocket is identified by virtual screening. Pharmacological and genetic inhibition of KDM4A/KDM4B significantly blocks the viability of cultured prostate cancer cells, which is accompanied by increased H3K9me3 staining and transcriptional silencing of growth-related genes. Significantly, a substantial portion of differentially expressed genes are AR-responsive, consistent with the roles of KDM4s as critical AR activators. Our results point to KDM4 as a useful therapeutic target and identify a new inhibitor scaffold.
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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.