ArticleACS chemical biology2016
Deazaflavin Inhibitors of Tyrosyl-DNA Phosphodiesterase 2 (TDP2) Specific for the Human Enzyme and Active against Cellular TDP2.
Article in ACS chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Article
- New Hybrid Compounds Combining Fragments of Usnic Acid and Thioether Are Inhibitors of Human Enzymes TDP1, TDP2 and PARP1.International journal of molecular sciences · 2021Article
- The synthesis of furoquinolinedione and isoxazoloquinolinedione derivatives as selective Tyrosyl-DNA phosphodiesterase 2 (TDP2) inhibitors.Bioorganic chemistry · 2021Article
- Exonuclease VII repairs quinolone-induced damage by resolving DNA gyrase cleavage complexes.Science advances · 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
- Novel deazaflavin tyrosyl-DNA phosphodiesterase 2 (TDP2) inhibitors.DNA repair · 2020Article
- 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
- DNA protein crosslink proteolysis repair: From yeast to premature ageing and cancer in humans.DNA repair · 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
- Synthesis and structure-activity relationship of furoquinolinediones as inhibitors of Tyrosyl-DNA phosphodiesterase 2 (TDP2).European journal of medicinal chemistry · 2018Article
- Mitochondrial tyrosyl-DNA phosphodiesterase 2 and its TDP2EMBO reports · 2018Article
- Tyrosyl-DNA phosphodiesterases: rescuing the genome from the risks of relaxation.Nucleic acids research · 2018Review
- ZATT (ZNF451)-mediated resolution of topoisomerase 2 DNA-protein cross-links.Science (New York, N.Y.) · 2017Article
- Targeting DNA repair and replication stress in the treatment of ovarian cancer.International journal of clinical oncology · 2017Review
- Long-term hepatitis B infection in a scalable hepatic co-culture system.Nature communications · 2017Article
- Synthesis and Biological Evaluation of the First Triple Inhibitors of Human Topoisomerase 1, Tyrosyl-DNA Phosphodiesterase 1 (Tdp1), and Tyrosyl-DNA Phosphodiesterase 2 (Tdp2).Journal of medicinal chemistry · 2017Article
- Discovery of selective inhibitors of tyrosyl-DNA phosphodiesterase 2 by targeting the enzyme DNA-binding cleft.Bioorganic & medicinal chemistry letters · 2016Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Tyrosyl-DNA phosphodiesterase 2 repairs irreversible topoisomerase II-mediated cleavage complexes generated by anticancer topoisomerase-targeted drugs and processes replication intermediates for picornaviruses (VPg unlinkase) and hepatitis B virus. There is currently no TDP2 inhibitor in clinical development. Here, we report a series of deazaflavin derivatives that selectively inhibit the human TDP2 enzyme in a competitive manner both with recombinant and native TDP2. We show that mouse, fish, and C. elegans TDP2 enzymes are highly resistant to the drugs and that key protein residues are responsible for drug resistance. Among them, human residues L313 and T296 confer high resistance when mutated to their mouse counterparts. Moreover, deazaflavin derivatives show potent synergy in combination with the topoisomerase II inhibitor etoposide in human prostate cancer DU145 cells and TDP2-dependent synergy in TK6 human lymphoblast and avian DT40 cells. Deazaflavin derivatives represent the first suitable platform for the development of potent and selective TDP2 inhibitors.
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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.