ArticleThe Journal of biological chemistry2015
New insights on the mechanism of quinoline-based DNA Methyltransferase inhibitors.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 68 citations in OpenAlex.
- Recent Advances in Searching for DNMT Inhibitors and Their Potential Application in Treating Human Diseases.International journal of molecular sciences · 2026Review
- HIF-activated priming of TRAIL-induced cell death determines epigenetic vulnerability in kidney cancer.Cell reports. Medicine · 2026Article
- Quinoline-Based DNA Methyltransferase Inhibitors Featuring Basic Side Chains: Design, Synthesis, and Insight in Biochemical and Anticancer Cell Properties.Journal of medicinal chemistry · 2025Article
- MDM2 and DNMT1 inhibitors induce neuroblastoma cell death through p53-dependent and independent pathways.Epigenomics · 2025Article
- Epigenetic control in thyroid cancer: mechanisms and clinical perspective.Cell death discovery · 2025Review
- An all-in-one pipeline for the in vitro discovery and in vivo testing of Plasmodium falciparum malaria transmission blocking drugs.Nature communications · 2025Article
- Efficacy of graphene quantum dot-hyaluronic acid nanocomposites containing quinoline for target therapy against cancer cells.Scientific reports · 2025Article
- Significance of targeting DNMT3A mutations in AML.Annals of hematology · 2025Review
- The power and the promise of epigenetic drugs in oncology.Frontiers in genetics · 2025Review
- Quinoline-based compounds can inhibit diverse enzymes that act on DNA.Cell chemical biology · 2024Article
- De Novo Design of Inhibitors of DNA Methyltransferase 1: A Critical Comparison of Ligand- and Structure-Based Approaches.Biomolecules · 2024Article
- DNA Methyltransferase 3A: A Significant Target for the Discovery of Inhibitors as Potent Anticancer Drugs.Mini reviews in medicinal chemistry · 2024Review
- GSK-3484862 targets DNMT1 for degradation in cells.NAR cancer · 2023Article
- Structural characterization of dicyanopyridine containing DNMT1-selective, non-nucleoside inhibitors.Structure (London, England : 1993) · 2022Article
- 7-Aminoalkoxy-Quinazolines from Epigenetic Focused Libraries Are Potent and Selective Inhibitors of DNA Methyltransferase 1.Molecules (Basel, Switzerland) · 2022Article
- Inhibitors of DNA Methylation.Advances in experimental medicine and biology · 2022Review
- Novel Targeting of DNA Methyltransferase Activity Inhibits Ewing Sarcoma Cell Proliferation and Enhances Tumor Cell Sensitivity to DNA Damaging Drugs by Activating the DNA Damage Response.Frontiers in endocrinology · 2022Article
- Discovery of a first-in-class reversible DNMT1-selective inhibitor with improved tolerability and efficacy in acute myeloid leukemia.Nature cancer · 2021Article
- Discovery of the first chemical tools to regulate MKK3-mediated MYC activation in cancer.Bioorganic & medicinal chemistry · 2021Article
- DNA methyltransferase inhibitors combination therapy for the treatment of solid tumor: mechanism and clinical application.Clinical epigenetics · 2021Review
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Among the epigenetic marks, DNA methylation is one of the most studied. It is highly deregulated in numerous diseases, including cancer. Indeed, it has been shown that hypermethylation of tumor suppressor genes promoters is a common feature of cancer cells. Because DNA methylation is reversible, the DNA methyltransferases (DNMTs), responsible for this epigenetic mark, are considered promising therapeutic targets. Several molecules have been identified as DNMT inhibitors and, among the non-nucleoside inhibitors, 4-aminoquinoline-based inhibitors, such as SGI-1027 and its analogs, showed potent inhibitory activity. Here we characterized the in vitro mechanism of action of SGI-1027 and two analogs. Enzymatic competition studies with the DNA substrate and the methyl donor cofactor, S-adenosyl-l-methionine (AdoMet), displayed AdoMet non-competitive and DNA competitive behavior. In addition, deviations from the Michaelis-Menten model in DNA competition experiments suggested an interaction with DNA. Thus their ability to interact with DNA was established; although SGI-1027 was a weak DNA ligand, analog 5, the most potent inhibitor, strongly interacted with DNA. Finally, as 5 interacted with DNMT only when the DNA duplex was present, we hypothesize that this class of chemical compounds inhibit DNMTs by interacting with the DNA substrate.
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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.