ArticleNucleic acids research2019
Identification of a ligand binding hot spot and structural motifs replicating aspects of tyrosyl-DNA phosphodiesterase I (TDP1) phosphoryl recognition by crystallographic fragment cocktail screening.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 25 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
- Ultra-large library screening with an evolutionary algorithm in Rosetta (REvoLd).Communications chemistry · 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
- Unveiling the multifaceted domain polymorphism of the Menshen antiphage system.Nucleic acids research · 2025Article
- Targeted sulfur(VI) fluoride exchange-mediated covalent modification of a tyrosine residue in the catalytic pocket of tyrosyl-DNA phosphodiesterase 1.Communications chemistry · 2024Article
- Article
- Identification of multidentate tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibitors that simultaneously access the DNA, protein and catalytic-binding sites by oxime diversification.RSC chemical biology · 2023Article
- Synthesis of 11-aminoalkoxy substituted benzophenanthridine derivatives as tyrosyl-DNA phosphodiesterase 1 inhibitors and their anticancer activity.Bioorganic chemistry · 2022Article
- Pyranodipyran Derivatives with Tyrosyl DNA Phosphodiesterase 1 Inhibitory Activities and Fluorescent Properties fromMarine drugs · 2022Article
- Phosphonic acid-containing inhibitors of tyrosyl-DNA phosphodiesterase 1.Frontiers in chemistry · 2022Article
- Validating TDP1 as an Inhibition Target for the Development of Chemosensitizers for Camptothecin-Based Chemotherapy Drugs.Oncology and therapy · 2021Article
- Identification and confirmation of 14-3-3 ζ as a novel target of ginsenosides in brain tissues.Journal of ginseng research · 2021Article
- Novel Tdp1 Inhibitors Based on Adamantane Connected with Monoterpene Moieties via Heterocyclic Fragments.Molecules (Basel, Switzerland) · 2021Article
- Critical roles of Rad54 in tolerance to apigenin-induced Top1-mediated DNA damage.Experimental and therapeutic medicine · 2021Article
- Discovery of Novel Sultone Fused Berberine Derivatives as Promising Tdp1 Inhibitors.Molecules (Basel, Switzerland) · 2021Article
- Small molecule microarray identifies inhibitors of tyrosyl-DNA phosphodiesterase 1 that simultaneously access the catalytic pocket and two substrate binding sites.Chemical science · 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
- The First Berberine-Based Inhibitors of Tyrosyl-DNA Phosphodiesterase 1 (Tdp1), an Important DNA Repair Enzyme.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Tyrosyl DNA-phosphodiesterase I (TDP1) repairs type IB topoisomerase (TOP1) cleavage complexes generated by TOP1 inhibitors commonly used as anticancer agents. TDP1 also removes DNA 3' end blocking lesions generated by chain-terminating nucleosides and alkylating agents, and base oxidation both in the nuclear and mitochondrial genomes. Combination therapy with TDP1 inhibitors is proposed to synergize with topoisomerase targeting drugs to enhance selectivity against cancer cells exhibiting deficiencies in parallel DNA repair pathways. A crystallographic fragment screening campaign against the catalytic domain of TDP1 was conducted to identify new lead compounds. Crystal structures revealed two fragments that bind to the TDP1 active site and exhibit inhibitory activity against TDP1. These fragments occupy a similar position in the TDP1 active site as seen in prior crystal structures of TDP1 with bound vanadate, a transition state mimic. Using structural insights into fragment binding, several fragment derivatives have been prepared and evaluated in biochemical assays. These results demonstrate that fragment-based methods can be a highly feasible approach toward the discovery of small-molecule chemical scaffolds to target TDP1, and for the first time, we provide co-crystal structures of small molecule inhibitors bound to TDP1, which could serve for the rational development of medicinal TDP1 inhibitors.
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