ArticleNucleic acids research2007
Novel high-throughput electrochemiluminescent assay for identification of human tyrosyl-DNA phosphodiesterase (Tdp1) inhibitors and characterization of furamidine (NSC 305831) as an inhibitor of Tdp1.
Article in Nucleic acids research, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 108 citations in OpenAlex.
- Synthesis and Biological Evaluation of TDP1 Inhibitors Based on Coumarin and Monoterpenoid Fragments Conjoined by Heterocyclic Moieties.International journal of molecular sciences · 2026Article
- Validating TDP1 as an Inhibition Target for Lipophilic Nucleoside Derivative in Human Cells.International journal of molecular sciences · 2025Article
- Novel Peptide-Drug Conjugates with Dual Anticancer Activity.International journal of molecular sciences · 2024Article
- Cheminformatic Identification of Tyrosyl-DNA Phosphodiesterase 1 (Tdp1) Inhibitors: A Comparative Study of SMILES-Based Supervised Machine Learning Models.Journal of personalized medicine · 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
- Unprecedented reactivity of polyamines with aldehydic DNA modifications: structural determinants of reactivity, characterization and enzymatic stability of adducts.Nucleic acids research · 2023Article
- Natural Products and Their Derivatives as Inhibitors of the DNA Repair Enzyme Tyrosyl-DNA Phosphodiesterase 1.International journal of molecular sciences · 2023Review
- Synthesis of 11-aminoalkoxy substituted benzophenanthridine derivatives as tyrosyl-DNA phosphodiesterase 1 inhibitors and their anticancer activity.Bioorganic chemistry · 2022Article
- Adamantane-Monoterpenoid Conjugates Linked via Heterocyclic Linkers Enhance the Cytotoxic Effect of Topotecan.Molecules (Basel, Switzerland) · 2022Article
- In Vitro and In Silico Studies of Human Tyrosyl-DNA Phosphodiesterase 1 (Tdp1) Inhibition by Stereoisomeric Forms of Lipophilic Nucleosides: The Role of Carbohydrate Stereochemistry in Ligand-Enzyme Interactions.Molecules (Basel, Switzerland) · 2022Article
- New Deoxycholic Acid Derived Tyrosyl-DNA Phosphodiesterase 1 Inhibitors Also Inhibit Tyrosyl-DNA Phosphodiesterase 2.Molecules (Basel, Switzerland) · 2021Article
- Inhibition of Arginine Methylation Impairs Platelet Function.ACS pharmacology & translational science · 2021Article
- Article
- A Dual-Sensor-Based Screening System for In Vitro Selection of TDP1 Inhibitors.Sensors (Basel, Switzerland) · 2021Article
- Novel Tdp1 Inhibitors Based on Adamantane Connected with Monoterpene Moieties via Heterocyclic Fragments.Molecules (Basel, Switzerland) · 2021Article
- Design, Synthesis, and Molecular Docking Study of New Tyrosyl-DNA Phosphodiesterase 1 (TDP1) Inhibitors Combining Resin Acids and Adamantane Moieties.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Design, Synthesis, and Biological Investigation of Novel Classes of 3-Carene-Derived Potent Inhibitors of TDP1.Molecules (Basel, Switzerland) · 2020Article
- Promising New Inhibitors of Tyrosyl-DNA Phosphodiesterase I (Tdp 1) Combining 4-Arylcoumarin and Monoterpenoid Moieties as Components of Complex Antitumor Therapy.International journal of molecular sciences · 2019Article
- Article
- Targeting Tyrosyl-DNA phosphodiesterase I to enhance toxicity of phosphodiester linked DNA-adducts.Cancer drug resistance (Alhambra, Calif.) · 2019Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
By enzymatically hydrolyzing the terminal phosphodiester bond at the 3'-ends of DNA breaks, tyrosyl-DNA phosphodiesterase (Tdp1) repairs topoisomerase-DNA covalent complexes and processes the DNA ends for DNA repair. To identify novel Tdp1 inhibitors, we developed a high-throughput assay that uses electrochemiluminescent (ECL) substrates. Subsequent to screening of 1981 compounds from the 'diversity set' of the NCI-Developmental Therapeutics Program, here we report that furamidine inhibits Tdp1 at low micromolar concentrations. Inhibition of Tdp1 by furamidine is effective both with single- and double-stranded substrates but is slightly stronger with the duplex DNA. Surface plasmon resonance studies show that furamidine binds both single- and double-stranded DNA, though more weakly with the single-stranded substrate DNA. Thus, the inhibition of Tdp1 activity could in part be due to the binding of furamidine to DNA. However, the inhibition of Tdp1 by furamidine is independent of the substrate DNA sequence. The kinetics of Tdp1 inhibition by furamidine was influenced by the drug to enzyme ratio and duration of the reaction. Comparison with related dications shows that furamidine inhibits Tdp1 more effectively than berenil, while pentamidine was inactive. Thus, furamidine represents the most potent Tdp1 inhibitor reported to date.
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