ArticleStructure (London, England : 1993)2022
Structural characterization of dicyanopyridine containing DNMT1-selective, non-nucleoside inhibitors.
Article in Structure (London, England : 1993), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Disease-Associated Mutations Impact DNA Methyltransferase 1 Function through Dynamic Allosteric Effects and Solvent Exposure.Journal of chemical theory and computation · 2026Article
- SUMOylation enhances DNMT1 function to repress mega-intergenic RNAs and viral mimicry.Nature genetics · 2026Article
- Recent Advances in Searching for DNMT Inhibitors and Their Potential Application in Treating Human Diseases.International journal of molecular sciences · 2026Review
- Structure-guided design of 7-azaindole DNMT1 inhibitors active against hypomethylating agent-resistant acute myeloid leukemia.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Single-molecule tracking of DNMT1 in living cells reveals its cell cycle dynamics and its redistribution upon drug treatment.Nucleic acids research · 2026Article
- Discovery of a Novel DNMT1 Inhibitor with Improved Efficacy in Treating β-Thalassemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- DNMT1/MTTP axis promotes gastritis progression duringEpigenomics · 2025Article
- DNA methylation protects cancer cells against senescence.Nature communications · 2025Article
- GSK-3484862, a DNMT1 degrader, promotesNAR cancer · 2025Article
- Quinoline-based compounds can inhibit diverse enzymes that act on DNA.Cell chemical biology · 2024Article
- Cytosine analogues as DNA methyltransferase substrates.Nucleic acids research · 2024Article
- C2H2 Zinc Finger Transcription Factors Associated with Hemoglobinopathies.Journal of molecular biology · 2024Review
- Article
- Methylation across the central dogma in health and diseases: new therapeutic strategies.Signal transduction and targeted therapy · 2023Review
- GSK-3484862 targets DNMT1 for degradation in cells.NAR cancer · 2023Article
- Systematic Design of Adenosine Analogs as Inhibitors of aJournal of medicinal chemistry · 2023Article
- Mediating and maintaining methylation while minimizing mutation: Recent advances on mammalian DNA methyltransferases.Current opinion in structural biology · 2022Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
DNMT1 maintains the parental DNA methylation pattern on newly replicated hemimethylated DNA. The failure of this maintenance process causes aberrant DNA methylation that affects transcription and contributes to the development and progression of cancers such as acute myeloid leukemia. Here, we structurally characterized a set of newly discovered DNMT1-selective, reversible, non-nucleoside inhibitors that bear a core 3,5-dicyanopyridine moiety, as exemplified by GSK3735967, to better understand their mechanism of inhibition. All of the dicyanopydridine-containing inhibitors examined intercalate into the hemimethylated DNA between two CpG base pairs through the DNA minor groove, resulting in conformational movement of the DNMT1 active-site loop. In addition, GSK3735967 introduces two new binding sites, where it interacts with and stabilizes the displaced DNMT1 active-site loop and it occupies an open aromatic cage in which trimethylated histone H4 lysine 20 is expected to bind. Our work represents a substantial step in generating potent, selective, and non-nucleoside inhibitors of DNMT1.
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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.