ArticleNature chemical biology2016
Cellularly active N-hydroxyurea FEN1 inhibitors block substrate entry to the active site.
Article in Nature chemical biology, 2016. 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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Who cites it
42 citing papers in PubMed, 75 citations in OpenAlex.
- Evolving CRBN ligands enhance the drug-like properties of protein degraders.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Integrated Genetic Screening Identifies FEN1 as a Selective Vulnerability and Temozolomide Resistance Mediator in Glioblastoma Stem Cells.Cancer research communications · 2026Article
- Functional roles for FEN1 phosphate steering residues in multi-step substrate verification prior to reaction.The Journal of biological chemistry · 2026Article
- XPF mediates 3' flap processing for FEN1-independent Okazaki fragment maturation.Nucleic acids research · 2026Article
- PARP1-mediated 5' flap dynamics facilitate Okazaki fragment maturation.bioRxiv : the preprint server for biology · 2026Article
- MDC1 counteracts replication fork reversal and mediates chemosensitivity in BRCA1/2-deficient tumors.Oncogene · 2026Article
- Long-Patch Base Excision Repair of 5'-DNA-Peptide Cross-Links Derived from Abasic DNA Lesions.Biochemistry · 2026Article
- Mechanistic insights into the monotherapy and combination potential of FEN1 inhibition in cancer therapy.Nucleic acids research · 2025Article
- XPF mediates 3' flap processing for FEN1-independent Okazaki fragment maturation.bioRxiv : the preprint server for biology · 2025Article
- Barcode-free hit discovery from massive libraries enabled by automated small molecule structure annotation.Nature communications · 2025Article
- FEN1 is critical for rapid single-strand break repair in G1 phase.Nucleic acids research · 2025Article
- Targeting FEN1/EXO1 to enhance efficacy of PARP inhibition in triple-negative breast cancer.Translational oncology · 2025Article
- Article
- DNA lesions can frequently precede DNA:RNA hybrid accumulation.Nature communications · 2025Article
- Discovery of Substituted 5-(2-Hydroxybenzoyl)-2-Pyridone Analogues as Inhibitors of the Human Caf1/CNOT7 Ribonuclease.Molecules (Basel, Switzerland) · 2024Article
- Cell-active small molecule inhibitors validate the SNM1A DNA repair nuclease as a cancer target.Chemical science · 2024Article
- DNA combing versus DNA spreading and the separation of sister chromatids.The Journal of cell biology · 2024Article
- PARG-deficient tumor cells have an increased dependence on EXO1/FEN1-mediated DNA repair.The EMBO journal · 2024Article
- Oxidized DNA fragments exit mitochondria via mPTP- and VDAC-dependent channels to activate NLRP3 inflammasome and interferon signaling.Immunity · 2022Article
- Characterization of the SARS-CoV-2 ExoN (nsp14ExoN-nsp10) complex: implications for its role in viral genome stability and inhibitor identification.Nucleic acids research · 2022Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
The structure-specific nuclease human flap endonuclease-1 (hFEN1) plays a key role in DNA replication and repair and may be of interest as an oncology target. We present the crystal structure of inhibitor-bound hFEN1, which shows a cyclic N-hydroxyurea bound in the active site coordinated to two magnesium ions. Three such compounds had similar IC50 values but differed subtly in mode of action. One had comparable affinity for protein and protein-substrate complex and prevented reaction by binding to active site catalytic metal ions, blocking the necessary unpairing of substrate DNA. Other compounds were more competitive with substrate. Cellular thermal shift data showed that both inhibitor types engaged with hFEN1 in cells, and activation of the DNA damage response was evident upon treatment with inhibitors. However, cellular EC50 values were significantly higher than in vitro inhibition constants, and the implications of this for exploitation of hFEN1 as a drug target are discussed.
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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.