ArticleHaematologica2021
Article in Haematologica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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.
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Who cites it
42 citing papers in PubMed, 66 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
- Reduced Maintenance DNA Methylation Thresholds Enable Sensitive Reporter Assays for UHRF1 and DNMT1 Inhibition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeted protein degradation for fetal hemoglobin induction: a new paradigm in β-hemoglobinopathy therapy.Biomarker research · 2026Review
- Regulation of BCL11A DNA binding and expression in human erythrocyte precursor HUDEP-2 cells.bioRxiv : the preprint server for biology · 2026Article
- Discovery of a Novel DNMT1 Inhibitor with Improved Efficacy in Treating β-Thalassemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Epigenetic Reprogramming of Erythroid Progenitor Cells: Insights for Enhancing Cancer Immunotherapy.International journal of biological sciences · 2026Review
- Comprehensive regulation of γ-globin expression by epigenetic modifications and protein post-translational modifications.Clinical epigenetics · 2025Review
- Dual EZH1/2 inhibition enhances DNMT inhibitor efficacy in colon cancer through targeting H3K27me1.bioRxiv : the preprint server for biology · 2025Article
- Article
- Epigenetic Regulation of Erythropoiesis: From Developmental Programs to Therapeutic Targets.International journal of molecular sciences · 2025Review
- GSK-3484862, a DNMT1 degrader, promotesNAR cancer · 2025Article
- The induction effect of hydroxyurea and metformin on fetal globin in the K562 cell line.Molecular medicine (Cambridge, Mass.) · 2025Article
- Structure-Activity Relationship Studies of DNA Methyltransferase 1 Monovalent Degraders.Journal of medicinal chemistry · 2025Article
- Genetic Modifiers of Hemoglobin Expression from a Clinical Perspective in Hemoglobinopathy Patients with Beta Thalassemia and Sickle Cell Disease.International journal of molecular sciences · 2024Review
- DNMT1 regulates human erythropoiesis by modulating cell cycle and endoplasmic reticulum stress in a stage-specific manner.Cell death and differentiation · 2024Article
- Review
- C2H2 Zinc Finger Transcription Factors Associated with Hemoglobinopathies.Journal of molecular biology · 2024Review
- The molecular basis of cell memory in mammals: The epigenetic cycle.Science advances · 2024Review
- GSK-3484862 targets DNMT1 for degradation in cells.NAR cancer · 2023Article
- Fetal hemoglobin level predicts lower-risk myelodysplastic syndrome.International journal of hematology · 2023Article
Corrections and comments
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Authors and funding
23 authors at 3 institutions in 2 countries.
Funding
Abstract
Pharmacological induction of fetal hemoglobin (HbF) expression is an effective therapeutic strategy for the management of beta-hemoglobinopathies such as sickle cell disease. DNA methyltransferase (DNMT) inhibitors 5-azacytidine (5-aza) and 5-aza-2'-deoxycytidine (decitabine) have been shown to induce fetal hemoglobin expression in both preclinical models and clinical studies, but are not currently approved for the management of hemoglobinopathies. We report here the discovery of a novel class of orally bioavailable DNMT1-selective inhibitors as exemplified by GSK3482364. This molecule potently inhibits the methyltransferase activity of DNMT1, but not DNMT family members DNMT3A or DNMT3B. In contrast with cytidine analog DNMT inhibitors, the DNMT1 inhibitory mechanism of GSK3482364 does not require DNA incorporation and is reversible. In cultured human erythroid progenitor cells (EPCs), GSK3482364 decreased overall DNA methylation resulting in de-repression of the gamma globin genes HBG1 and HBG2 and increased HbF expression. In a transgenic mouse model of sickle cell disease, orally administered GSK3482364 caused significant increases in both HbF levels and in the percentage HbF-expressing erythrocytes, with good overall tolerability. We conclude that in these preclinical models, selective, reversible inhibition of DNMT1 is sufficient for the induction of HbF, and is well-tolerated. We anticipate that GSK3482364 will be a useful tool molecule for the further study of selective DNMT1 inhibition both in vitro and in vivo.
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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.