ArticleMolecular cancer therapeutics2006
A novel norindenoisoquinoline structure reveals a common interfacial inhibitor paradigm for ternary trapping of the topoisomerase I-DNA covalent complex.
Article in Molecular cancer therapeutics, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 162 citations in OpenAlex.
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- Topoisomerase Assays.Current protocols · 2021Article
- Three different mutations in the DNA topoisomerase 1B in Leishmania infantum contribute to resistance to antitumor drug topotecan.Parasites & vectors · 2021Article
- Hybrid Quinolinyl Phosphonates as Heterocyclic Carboxylate Isosteres: Synthesis and Biological Evaluation against Topoisomerase 1B (TOP1B).Pharmaceuticals (Basel, Switzerland) · 2021Article
- Novel Tdp1 Inhibitors Based on Adamantane Connected with Monoterpene Moieties via Heterocyclic Fragments.Molecules (Basel, Switzerland) · 2021Article
- Article
- Recent developments in topoisomerase-targeted cancer chemotherapy.Acta pharmaceutica Sinica. B · 2018Review
- Characterization and structure-activity relationships of indenoisoquinoline-derived topoisomerase I inhibitors in unsilencing the dormantMolecular autism · 2018Article
- Design and Synthesis of Chlorinated and Fluorinated 7-Azaindenoisoquinolines as Potent Cytotoxic Anticancer Agents That Inhibit Topoisomerase I.Journal of medicinal chemistry · 2017Article
- Synthesis and biological evaluation of new carbohydrate-substituted indenoisoquinoline topoisomerase I inhibitors and improved syntheses of the experimental anticancer agents indotecan (LMP400) and indimitecan (LMP776).Journal of medicinal chemistry · 2014Article
- Development of purely structure-based pharmacophores for the topoisomerase I-DNA-ligand binding pocket.Journal of computer-aided molecular design · 2013Article
- Three missense mutations of DNA topoisomerase I in highly camptothecin-resistant colon cancer cell sublines.Oncology reports · 2013Article
- 6-Amino-2-methyl-8-phenyl-1,2,3,4-tetra-hydro-iso-quinoline-5,7-dicarbo-nitrile.Acta crystallographica. Section E, Structure reports online · 2013Article
- Drugging topoisomerases: lessons and challenges.ACS chemical biology · 2013Review
- Solvent dependency of the UV-Vis spectrum of indenoisoquinolines: role of keto-oxygens as polarity interaction probes.PloS one · 2013Article
- Article
- Interfacial inhibitors: targeting macromolecular complexes.Nature reviews. Drug discovery · 2011Review
- Tyrosyl-DNA Phosphodiesterase 1 (Tdp1) inhibitors.Expert opinion on therapeutic patents · 2011Review
- Molecular and cellular pharmacology of the novel noncamptothecin topoisomerase I inhibitor Genz-644282.Molecular cancer therapeutics · 2011Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
We show that five topoisomerase I inhibitors (two indenoisoquinolines, two camptothecins, and one indolocarbazole) each intercalate between the base pairs flanking the cleavage site generated during the topoisomerase I catalytic cycle and are further stabilized by a network of hydrogen bonds with topoisomerase I. The interfacial inhibition paradigm described for topoisomerase I inhibitors can be generalized to a variety of natural products that trap macromolecular complexes as they undergo catalytic conformational changes that create hotspots for drug binding. Stabilization of such conformational states results in uncompetitive inhibition and exemplifies the relevance of screening for ligands and drugs that stabilize ("trap") these macromolecular complexes.
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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.