ArticleSLAS discovery : advancing life sciences R & D2017
Identification of Natural Products That Inhibit the Catalytic Function of Human Tyrosyl-DNA Phosphodiesterase (TDP1).
Article in SLAS discovery : advancing life sciences R & D, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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The trial behind it
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
14 citing papers in PubMed, 21 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
- The Influence of TDP1 Inhibitor Usnic Acid Derivative OL9-116 on the Effects of Topotecan in Human Cells.Current issues in molecular biology · 2026Article
- Validating TDP1 as an Inhibition Target for Lipophilic Nucleoside Derivative in Human Cells.International journal of molecular sciences · 2025Article
- Potent β-lactam-based tyrosyl-DNA phosphodiesterase 1 inhibitors identified by a virtual screen.Scientific reports · 2025Article
- Application of a bivalent "click" approach to target tyrosyl-DNA phosphodiesterase 1 (TDP1).RSC medicinal chemistry · 2025Article
- Novel Peptide-Drug Conjugates with Dual Anticancer Activity.International journal of molecular sciences · 2024Article
- Targeted sulfur(VI) fluoride exchange-mediated covalent modification of a tyrosine residue in the catalytic pocket of tyrosyl-DNA phosphodiesterase 1.Communications chemistry · 2024Article
- Natural Products and Their Derivatives as Inhibitors of the DNA Repair Enzyme Tyrosyl-DNA Phosphodiesterase 1.International journal of molecular sciences · 2023Review
- A Dual-Sensor-Based Screening System for In Vitro Selection of TDP1 Inhibitors.Sensors (Basel, Switzerland) · 2021Article
- Recifin A, Initial Example of the Tyr-Lock Peptide Structural Family, Is a Selective Allosteric Inhibitor of Tyrosyl-DNA Phosphodiesterase I.Journal of the American Chemical Society · 2020Article
- Creating and screening natural product libraries.Natural product reports · 2020Review
- Natural Products as a Foundation for Drug Discovery.Current protocols in pharmacology · 2019Review
- NCI Program for Natural Product Discovery: A Publicly-Accessible Library of Natural Product Fractions for High-Throughput Screening.ACS chemical biology · 2018Article
- Tyrosyl-DNA phosphodiesterases: rescuing the genome from the risks of relaxation.Nucleic acids research · 2018Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
Tyrosyl-DNA phosphodiesterase 1 (TDP1) is an enzyme crucial for cleavage of the covalent topoisomerase 1-DNA complex, an intermediate in DNA repair. TDP1 plays a role in reversing inhibition of topoisomerase I by camptothecins, a series of potent and effective inhibitors used in the treatment of colorectal, ovarian, and small-cell lung cancers. It is hypothesized that inhibition of TDP1 activity may enhance camptothecin sensitivity in tumors. Here, we describe the design, development, and execution of a novel assay to identify inhibitors of TDP1 present in natural product extracts. The assay was designed to address issues with fluorescent "nuisance" molecules and to minimize the detection of false-positives caused by polyphenolic molecules known to nonspecifically inhibit enzyme activity. A total of 227,905 purified molecules, prefractionated extracts, and crude natural product extracts were screened. This yielded 534 initial positives (0.23%). Secondary prioritization reduced this number to 117 (0.05% final hit rate). Several novel inhibitors have been identified showing micromolar affinity for human TDP1, including halenaquinol sulfate, a pentacyclic hydroquinone from the sponge
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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.