ArticleCancer research2009
A new class of quinoline-based DNA hypomethylating agents reactivates tumor suppressor genes by blocking DNA methyltransferase 1 activity and inducing its degradation.
Article in Cancer research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 101 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
101 citing papers in PubMed, 264 citations in OpenAlex.
- Discovery of a Novel DNMT1 Inhibitor with Improved Efficacy in Treating β-Thalassemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- MDM2 and DNMT1 inhibitors induce neuroblastoma cell death through p53-dependent and independent pathways.Epigenomics · 2025Article
- An all-in-one pipeline for the in vitro discovery and in vivo testing of Plasmodium falciparum malaria transmission blocking drugs.Nature communications · 2025Article
- Design, synthesis and evaluation of pyrimidinobenzylamide and pyrimidinothiophenamide derivatives as inhibitors of DOT1L and related epigenetic targets DNMT3a, PRMT4 and other HMTs.RSC medicinal chemistry · 2025Article
- Advances in epigenetic treatment of adult T-cell leukemia/lymphoma: a comprehensive review.Clinical epigenetics · 2025Review
- Fragment-based discovery of new potential DNMT1 inhibitors integrating multiple pharmacophore modeling, 3D-QSAR, virtual screening, molecular docking, ADME, and molecular dynamics simulation approaches.Molecular diversity · 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
- De Novo Design of Inhibitors of DNA Methyltransferase 1: A Critical Comparison of Ligand- and Structure-Based Approaches.Biomolecules · 2024Article
- Epigenetic regulation as a therapeutic target in the malaria parasite Plasmodium falciparum.Malaria journal · 2024Review
- Genome-wide identification of histone lysine methyltransferases and their implications in the epigenetic regulation of eggshell formation-related genes in a trematode parasite Clonorchis sinensis.Parasites, hosts and diseases · 2024Article
- Reshaping the Landscape of the Genome: Toolkits for Precise DNA Methylation Manipulation and Beyond.JACS Au · 2024Review
- Retraction: A New Class of Quinoline-Based DNA Hypomethylating Agents Reactivates Tumor Suppressor Genes by Blocking DNA Methyltransferase 1 Activity and Inducing Its Degradation.Cancer research · 2023Article
- Epidrugs as Promising Tools to EliminatePharmaceutics · 2023Article
- Exploring the dynamic interplay between cancer stem cells and the tumor microenvironment: implications for novel therapeutic strategies.Journal of translational medicine · 2023Review
- Insights into the Inhibitory Mechanisms of the Covalent Drugs for DNMT3A.International journal of molecular sciences · 2023Article
- Mechanistic Insights into Harmine-Mediated Inhibition of Human DNA Methyltransferases and Prostate Cancer Cell Growth.ACS chemical biology · 2023Article
- GSK-3484862 targets DNMT1 for degradation in cells.NAR cancer · 2023Article
- Design, synthesis, and biological evaluation of novel carbazole derivatives as potent DNMT1 inhibitors with reasonable PK properties.Journal of enzyme inhibition and medicinal chemistry · 2022Article
41 more citing papers are in PubMed but not listed here.
Corrections and comments
- Retraction · 2023-12-15Duplication of/in Image · Euphemisms for Duplication · Investigation by Company/Institution · Investigation by Journal/Publisher · Misconduct - Official Investigation(s) and/or Finding(s) · Misconduct by Author · Objections by Author(s) · · Samsom Jacob has institutional finding of misconduct;
- Retracted
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Reactivation of silenced tumor suppressor genes by 5-azacytidine (Vidaza) and its congener 5-aza-2'-deoxycytidine (decitabine) has provided an alternate approach to cancer therapy. We have shown previously that these drugs selectively and rapidly induce degradation of the maintenance DNA methyltransferase (DNMT) 1 by a proteasomal pathway. Because the toxicity of these compounds is largely due to their incorporation into DNA, it is critical to explore novel, nonnucleoside compounds that can effectively reactivate the silenced genes. Here, we report that a quinoline-based compound, designated SGI-1027, inhibits the activity of DNMT1, DNMT3A, and DNMT3B as well M. SssI with comparable IC(50) (6-13 micromol/L) by competing with S-adenosylmethionine in the methylation reaction. Treatment of different cancer cell lines with SGI-1027 resulted in selective degradation of DNMT1 with minimal or no effects on DNMT3A and DNMT3B. At a concentration of 2.5 to 5 micromol/L (similar to that of decitabine), complete degradation of DNMT1 protein was achieved within 24 h without significantly affecting its mRNA level. MG132 blocked SGI-1027-induced depletion of DNMT1, indicating the involvement of proteasomal pathway. Prolonged treatment of RKO cells with SGI-1027 led to demethylation and reexpression of the silenced tumor suppressor genes P16, MLH1, and TIMP3. Further, this compound did not exhibit significant toxicity in a rat hepatoma (H4IIE) cell line. This study provides a novel class of DNA hypomethylating agents that have the potential for use in epigenetic cancer therapy.
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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.