ArticleThe Biochemical journal2016
Mode of action of DNA-competitive small molecule inhibitors of tyrosyl DNA phosphodiesterase 2.
Article in The Biochemical journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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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
24 citing papers in PubMed, 37 citations in OpenAlex.
- CRAMP1-dependent histone H1 biogenesis is essential for topoisomerase II inhibitor tolerance.Molecular cell · 2025Article
- Article
- Osmotic disruption of chromatin induces Topoisomerase 2 activity at sites of transcriptional stress.Nature communications · 2024Article
- New Dual Inhibitors of Tyrosyl-DNA Phosphodiesterase 1 and 2 Based on Deoxycholic Acid: Design, Synthesis, Cytotoxicity, and Molecular Modeling.Molecules (Basel, Switzerland) · 2024Article
- CC-seq: Nucleotide-Resolution Mapping of Spo11 DNA Double-Strand Breaks in S. cerevisiae Cells.Methods in molecular biology (Clifton, N.J.) · 2024Article
- New Deoxycholic Acid Derived Tyrosyl-DNA Phosphodiesterase 1 Inhibitors Also Inhibit Tyrosyl-DNA Phosphodiesterase 2.Molecules (Basel, Switzerland) · 2021Article
- Radiosensitizer Effect of β-Apopicropodophyllin against Colorectal Cancer via Induction of Reactive Oxygen Species and Apoptosis.International journal of molecular sciences · 2021Article
- The synthesis of furoquinolinedione and isoxazoloquinolinedione derivatives as selective Tyrosyl-DNA phosphodiesterase 2 (TDP2) inhibitors.Bioorganic chemistry · 2021Article
- 4-Benzylideneisoquinoline-1,3(Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2021Article
- Identifying interactive biological pathways associated with reading disability.Brain and behavior · 2020Article
- Excision repair of topoisomerase DNA-protein crosslinks (TOP-DPC).DNA repair · 2020Review
- Molecular mechanisms of topoisomerase 2 DNA-protein crosslink resolution.Cellular and molecular life sciences : CMLS · 2020Review
- Novel deazaflavin tyrosyl-DNA phosphodiesterase 2 (TDP2) inhibitors.DNA repair · 2020Article
- A nucleotide resolution map of Top2-linked DNA breaks in the yeast and human genome.Nature communications · 2019Article
- Deazaflavin Inhibitors of TDP2 with Cellular Activity Can Affect Etoposide Influx and/or Efflux.ACS chemical biology · 2019Article
- Novel Deazaflavin Analogues Potently Inhibited Tyrosyl DNA Phosphodiesterase 2 (TDP2) and Strongly Sensitized Cancer Cells toward Treatment with Topoisomerase II (TOP2) Poison Etoposide.Journal of medicinal chemistry · 2019Article
- Triazolopyrimidine and triazolopyridine scaffolds as TDP2 inhibitors.Bioorganic & medicinal chemistry letters · 2019Article
- Crystal Structure of Human Nocturnin Catalytic Domain.Scientific reports · 2018Article
- Recent developments in topoisomerase-targeted cancer chemotherapy.Acta pharmaceutica Sinica. B · 2018Review
- New fluorescence-based high-throughput screening assay for small molecule inhibitors of tyrosyl-DNA phosphodiesterase 2 (TDP2).European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2018Article
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
Tyrosyl-DNA phosphodiesterase 2 (TDP2) is a 5'-tyrosyl DNA phosphodiesterase important for the repair of DNA adducts generated by non-productive (abortive) activity of topoisomerase II (TOP2). TDP2 facilitates therapeutic resistance to topoisomerase poisons, which are widely used in the treatment of a range of cancer types. Consequently, TDP2 is an interesting target for the development of small molecule inhibitors that could restore sensitivity to topoisomerase-directed therapies. Previous studies identified a class of deazaflavin-based molecules that showed inhibitory activity against TDP2 at therapeutically useful concentrations, but their mode of action was uncertain. We have confirmed that the deazaflavin series inhibits TDP2 enzyme activity in a fluorescence-based assay, suitable for high-throughput screen (HTS)-screening. We have gone on to determine crystal structures of these compounds bound to a 'humanized' form of murine TDP2. The structures reveal their novel mode of action as competitive ligands for the binding site of an incoming DNA substrate, and point the way to generating novel and potent inhibitors of TDP2.
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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.