ArticleJournal of medicinal chemistry2016
Isoquinoline-1,3-diones as Selective Inhibitors of Tyrosyl DNA Phosphodiesterase II (TDP2).
Article in Journal of medicinal chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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Who cites it
18 citing papers in PubMed, 66 citations in OpenAlex.
- Small-Molecule Activators of PRMT1: Discovery, SAR Analyses, and Proapoptotic Effects in Pancreatic Cancer Cells.Journal of medicinal chemistry · 2026Article
- Recent Advances in Synthetic Isoquinoline-Based Derivatives in Drug Design.Molecules (Basel, Switzerland) · 2025Review
- Photochemical Functionalization of 4‑Diazoisoquinoline-1,3(2ACS organic & inorganic Au · 2025Article
- New Deoxycholic Acid Derived Tyrosyl-DNA Phosphodiesterase 1 Inhibitors Also Inhibit Tyrosyl-DNA Phosphodiesterase 2.Molecules (Basel, Switzerland) · 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
- Enantioselective amination of 4-alkylisoquinoline-1,3(2RSC advances · 2020Article
- Novel deazaflavin tyrosyl-DNA phosphodiesterase 2 (TDP2) inhibitors.DNA repair · 2020Article
- Superelectrophiles in Synthesis: Preparation of Aromatic Imides.The Journal of organic chemistry · 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
- 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
- Tyrosyl-DNA phosphodiesterases: rescuing the genome from the risks of relaxation.Nucleic acids research · 2018Review
- Design, synthesis and biological evaluations of N-Hydroxy thienopyrimidine-2,4-diones as inhibitors of HIV reverse transcriptase-associated RNase H.European journal of medicinal chemistry · 2017Article
- Review
- Isoeugenol is a selective potentiator of camptothecin cytotoxicity in vertebrate cells lacking TDP1.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Tyrosyl DNA phosphodiesterase II (TDP2) is a recently discovered enzyme that specifically repairs DNA damages induced by topoisomerase II (Top2) poisons and causes resistance to these drugs. Inhibiting TDP2 is expected to enhance the efficacy of clinically important Top2-targeting anticancer drugs. However, TDP2 as a therapeutic target remains poorly understood. We report herein the discovery of isoquinoline-1,3-dione as a viable chemotype for selectively inhibiting TDP2. The initial hit compound 43 was identified by screening our in-house collection of synthetic compounds. Further structure-activity relationship (SAR) studies identified numerous analogues inhibiting TDP2 in low micromolar range without appreciable inhibition against the homologous TDP1 at the highest testing concentration (111 μM). The best compound 64 inhibited recombinant TDP2 with an IC50 of 1.9 μM. The discovery of this chemotype may provide a platform toward understanding TDP2 as a drug target.
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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.