ArticleScientific reports2021
Discovery of small molecules targeting the tandem tudor domain of the epigenetic factor UHRF1 using fragment-based ligand discovery.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Sodium Channel Blockers Demonstrate Binding Affinity for the Tandem Tudor Domain of the Epigenetic Hub UHRF1.ChemMedChem · 2026Article
- A New Recruitable E3 Ligase UHRF1 Supporting Targeted Protein Degradation: A Minimal Azide as a Recruitment Ligand.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Reduced Maintenance DNA Methylation Thresholds Enable Sensitive Reporter Assays for UHRF1 and DNMT1 Inhibition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Discovery and Characterization of Uracil Derivatives Targeting the Set-and-Ring Domain of UHRF1.Journal of chemical information and modeling · 2025Article
- Review
- E2F1 suppresses Epstein-Barr virus lytic reactivation through cellular and viral transcriptional networks.PLoS pathogens · 2025Article
- DNA methylation protects cancer cells against senescence.Nature communications · 2025Article
- Negative Cooperativity in the UHRF1 TTD-PHD Dual Domain Masks the Contributions of Cation-π Interactions between Trimethyllysine and the TTD Aromatic Cage.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- Oncogenic Roles of UHRF1 in Cancer.Epigenomes · 2024Review
- Non-canonical functions of UHRF1 maintain DNA methylation homeostasis in cancer cells.Nature communications · 2024Article
- Pharmacological perturbation of the phase-separating protein SMNDC1.Nature communications · 2023Article
- Natural and Synthetic Anticancer Epidrugs Targeting the Epigenetic Integrator UHRF1.Molecules (Basel, Switzerland) · 2023Review
- UHRF1 is a mediator of KRAS driven oncogenesis in lung adenocarcinoma.Nature communications · 2023Article
- E3 Ligases Meet Their Match: Fragment-Based Approaches to Discover New E3 Ligands and to Unravel E3 Biology.Journal of medicinal chemistry · 2023Review
- Protein arginine methylation in transcription and epigenetic regulation.Frontiers in epigenetics and epigenomics · 2023Review
- Large-Scale Chromatin Rearrangements in Cancer.Cancers · 2022Review
- Discovery and Mechanism of Small Molecule Inhibitors Selective for the Chromatin-Binding Domains of Oncogenic UHRF1.Biochemistry · 2022Article
- Inhibitors of DNA Methylation.Advances in experimental medicine and biology · 2022Review
- The multi-functionality of UHRF1: epigenome maintenance and preservation of genome integrity.Nucleic acids research · 2021Review
Corrections and comments
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Authors and funding
18 authors.
Funding
Abstract
Despite the established roles of the epigenetic factor UHRF1 in oncogenesis, no UHRF1-targeting therapeutics have been reported to date. In this study, we use fragment-based ligand discovery to identify novel scaffolds for targeting the isolated UHRF1 tandem Tudor domain (TTD), which recognizes the heterochromatin-associated histone mark H3K9me3 and supports intramolecular contacts with other regions of UHRF1. Using both binding-based and function-based screens of a ~ 2300-fragment library in parallel, we identified 2,4-lutidine as a hit for follow-up NMR and X-ray crystallography studies. Unlike previous reported ligands, 2,4-lutidine binds to two binding pockets that are in close proximity on TTD and so has the potential to be evolved into more potent inhibitors using a fragment-linking strategy. Our study provides a useful starting point for developing potent chemical probes against UHRF1.
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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.