ArticleClinical epigenetics2019
Identification of a novel quinoline-based DNA demethylating compound highly potent in cancer cells.
Article in Clinical epigenetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 51 citations in OpenAlex.
- DNA methyltransferase inhibitors in oncology: clinical progress, limitations and future directions.Epigenomics · 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
- 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
- Epigenetic Cancer Therapy.Indian journal of surgical oncology · 2024Article
- KDM5 family as therapeutic targets in breast cancer: Pathogenesis and therapeutic opportunities and challenges.Molecular cancer · 2024Review
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- Current Advances in Breast Cancer: Implications for Developing New Treatment Strategies Through Epi-Drugs on the Road to Modifying the Epigenome.Journal of clinical practice and research · 2023Review
- GSK-3484862 targets DNMT1 for degradation in cells.NAR cancer · 2023Article
- Correction: Identification of a novel quinoline-based DNA demethylating compound highly potent in cancer cells.Clinical epigenetics · 2022Article
- DNA Methyltransferases: From Evolution to Clinical Applications.International journal of molecular sciences · 2022Review
- Structural characterization of dicyanopyridine containing DNMT1-selective, non-nucleoside inhibitors.Structure (London, England : 1993) · 2022Article
- Lupus nephritis: The regulatory interplay between epigenetic and MicroRNAs.Frontiers in physiology · 2022Review
- DNA methyltransferase inhibitors combination therapy for the treatment of solid tumor: mechanism and clinical application.Clinical epigenetics · 2021Review
- Epigenetic-Based Therapy-A Prospective Chance for Medulloblastoma Patients' Recovery.International journal of molecular sciences · 2021Review
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Corrections and comments
- Erratum issued
Authors and funding
21 authors at 10 institutions in 5 countries.
Funding
Abstract
backgroundDNA methyltransferases (DNMTs) are epigenetic enzymes involved in embryonic development, cell differentiation, epithelial to mesenchymal transition, and control of gene expression, whose overexpression or enhanced catalytic activity has been widely reported in cancer initiation and progression. To date, two DNMT inhibitors (DNMTi), 5-azacytidine (5-AZA) and 5-aza-2'-deoxycytidine (DAC), are approved for the treatment of myelodysplastic syndromes and acute myeloid leukemia. Nevertheless, they are chemically instable and quite toxic for healthy cells; thus, the discovery of novel DNMTi is urgent.
resultsHere, we report the identification of a new quinoline-based molecule, MC3353, as a non-nucleoside inhibitor and downregulator of DNMT. This compound was able, in promoter demethylating assays, to induce enhanced green fluorescence protein (EGFP) gene expression in HCT116 cells and transcription in a cytomegalovirus (CMV) promoter-driven luciferase reporter system in KG-1 cells. Moreover, MC3353 displayed a strong antiproliferative activity when tested on HCT116 colon cancer cells after 48 h of treatment at 0.5 μM. At higher doses, this compound provided a cytotoxic effect in double DNMT knockout HCT116 cells. MC3353 was also screened on a different panel of cancer cells (KG-1 and U-937 acute myeloid leukemia, RAJI Burkitt's lymphoma, PC-3 prostate cancer, and MDA-MB-231 breast cancer), where it arrested cell proliferation and reduced viability after 48 h of treatment with IC
conclusionsThe present work describes MC3353 as a novel DNMTi displaying a stronger in cell demethylating ability than both 5-AZA and DAC, providing re-activation of the silenced ubiquitin C-terminal hydrolase L1 (UCHL1) gene. MC3353 displayed dose- and time-dependent antiproliferative activity in several cancer cell types, inducing cell death and affecting EMT through E-cadherin and MMP2 modulation. In addition, this compound proved efficacy even in primary osteosarcoma cell models, through the modulation of genes involved in osteoblast differentiation.
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