ArticleOncotarget2016
Screen-identified selective inhibitor of lysine demethylase 5A blocks cancer cell growth and drug resistance.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 85 citations in OpenAlex.
- Obesity Disrupts H3K4me3-Mediated Lactate Accumulation and Efferocytosis in Hypoxic Macrophages.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- KDM4B modulates ERα signaling pathway to participate in vascular smooth muscle cell calcification.Cell death discovery · 2025Article
- Roles of KDM5 demethylases in therapeutic resistance of cancers.Epigenetics & chromatin · 2025Review
- Histone demethylase inhibitors: developmental insights and current status.Future medicinal chemistry · 2025Review
- The KDM5A/HOXA5 axis regulates osteosarcoma progression via activating the Wnt/β-catenin pathway.European journal of medical research · 2025Article
- KDM5 family as therapeutic targets in breast cancer: Pathogenesis and therapeutic opportunities and challenges.Molecular cancer · 2024Review
- Cancer cell plasticity: from cellular, molecular, and genetic mechanisms to tumor heterogeneity and drug resistance.Cancer metastasis reviews · 2024Review
- Diapause-like Drug-Tolerant Persister State: The Key to Nirvana Rebirth.Medicina (Kaunas, Lithuania) · 2024Review
- MicroRNA-495: a therapeutic and diagnostic tumor marker.Journal of molecular histology · 2023Review
- Review
- Epigenetic markers and therapeutic targets for metastasis.Cancer metastasis reviews · 2023Review
- Knockdown of KDM5B Leads to DNA Damage and Cell Cycle Arrest in Granulosa Cells via MTF1.Current issues in molecular biology · 2023Article
- Targeting epigenetic regulators to overcome drug resistance in cancers.Signal transduction and targeted therapy · 2023Review
- KDM5 Lysine Demethylases in Pathogenesis, from Basic Science Discovery to the Clinic.Advances in experimental medicine and biology · 2023Article
- Biological Functions of the KDM2 Family of Histone Demethylases.Advances in experimental medicine and biology · 2023Article
- Advances in molecular characterization of pediatric acute megakaryoblastic leukemia not associated with Down syndrome; impact on therapy development.Frontiers in cell and developmental biology · 2023Review
- JMJD family proteins in cancer and inflammation.Signal transduction and targeted therapy · 2022Review
- CECR2 drives breast cancer metastasis by promoting NF-κB signaling and macrophage-mediated immune suppression.Science translational medicine · 2022Article
- Role of Nitric Oxide in Gene Expression Regulation during Cancer: Epigenetic Modifications and Non-Coding RNAs.International journal of molecular sciences · 2021Review
- KDM5A silencing transcriptionally suppresses the FXYD3-PI3K/AKT axis to inhibit angiogenesis in hepatocellular cancer via miR-433 up-regulation.Journal of cellular and molecular medicine · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Lysine demethylase 5A (KDM5A/RBP2/JARID1A) is a histone lysine demethylase that is overexpressed in several human cancers including lung, gastric, breast and liver cancers. It plays key roles in important cancer processes including tumorigenesis, metastasis, and drug tolerance, making it a potential cancer therapeutic target. Chemical tools to analyze KDM5A demethylase activity are extremely limited as available inhibitors are not specific for KDM5A. Here, we characterized KDM5A using a homogeneous luminescence-based assay and conducted a screen of about 9,000 small molecules for inhibitors. From this screen, we identified several 3-thio-1,2,4-triazole compounds that inhibited KDM5A with low μM in vitro IC50 values. Importantly, these compounds showed great specificity and did not inhibit its close homologue KDM5B (PLU1/JARID1B) or the related H3K27 demethylases KDM6A (UTX) and KDM6B (JMJD3). One compound, named YUKA1, was able to increase H3K4me3 levels in human cells and selectively inhibit the proliferation of cancer cells whose growth depends on KDM5A. As KDM5A was shown to mediate drug tolerance, we investigated the ability of YUKA1 to prevent drug tolerance in EGFR-mutant lung cancer cells treated with gefitinib and HER2+ breast cancer cells treated with trastuzumab. Remarkably, this compound hindered the emergence of drug-tolerant cells, highlighting the critical role of KDM5A demethylase activity in drug resistance. The small molecules presented here are excellent tool compounds for further study of KDM5A's demethylase activity and its contributions to cancer.
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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.