ArticleMolecular cancer therapeutics2018
Novel Fluoroindenoisoquinoline Non-Camptothecin Topoisomerase I Inhibitors.
Article in Molecular cancer therapeutics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
- Structural Mechanisms of Topoisomerase-Targeting Drugs.Annual review of biochemistry · 2025Review
- SLFN11-mediated ribosome biogenesis impairment induces TP53-independent apoptosis.Molecular cell · 2025Article
- Decarboxylative Aldol Reaction of α,α-Difluoro-β-keto Esters: Easy Access to Difluoroenolate.ACS omega · 2024Article
- Design, Synthesis, and Investigation of the Pharmacokinetics and Anticancer Activities of Indenoisoquinoline Derivatives That Stabilize the G-Quadruplex in theJournal of medicinal chemistry · 2024Article
- Structure-Activity Relationship of FL118 Platform Position 7 Versus Position 9-Derived Compounds and Their Mechanism of Action and Antitumor Activity.Journal of medicinal chemistry · 2023Article
- The crucial role of single-stranded DNA binding in enhancing sensitivity to DNA-damaging agents for Schlafen 11 and Schlafen 13.iScience · 2023Article
- Diphenyl ditelluride anticancer activity and DNA topoisomerase I poisoning in human colon cancer HCT116 cells.Oncotarget · 2023Article
- Next Generation Gold Drugs and Probes: Chemistry and Biomedical Applications.Chemical reviews · 2023Review
- Payload diversification: a key step in the development of antibody-drug conjugates.Journal of hematology & oncology · 2023Review
- 2-Arylquinolines as novel anticancer agents with dual EGFR/FAK kinase inhibitory activity: synthesis, biological evaluation, and molecular modelling insights.Journal of enzyme inhibition and medicinal chemistry · 2022Article
- Non-enzymatic function of WRN RECQL helicase regulates removal of topoisomerase-I-DNA covalent complexes and triggers NF-κB signaling in cancer.Aging cell · 2022Article
- Tricking enzymes in living cells: a mechanism-based strategy for design of DNA topoisomerase biosensors.Journal of nanobiotechnology · 2021Article
- Discovery of 4-alkoxy-2-aryl-6,7-dimethoxyquinolines as a new class of topoisomerase I inhibitors endowed with potent in vitro anticancer activity.European journal of medicinal chemistry · 2021Article
- Camptothecin Regulates Microglia Polarization and Exerts Neuroprotective EffectsFrontiers in immunology · 2021Article
- Epigenetic suppression of SLFN11 in germinal center B-cells during B-cell development.PloS one · 2021Article
- The Indenoisoquinoline LMP517: A Novel Antitumor Agent Targeting both TOP1 and TOP2.Molecular cancer therapeutics · 2020Article
- BRCAness, SLFN11, and RB1 loss predict response to topoisomerase I inhibitors in triple-negative breast cancers.Science translational medicine · 2020Article
- Identification of lamins as the molecular targets of LBL1 using a clickable photoaffinity probe.Methods in enzymology · 2020Article
- Lignin-Based Hollow Nanoparticles for Controlled Drug Delivery: Grafting Preparation Using β-Cyclodextrin/Enzymatic-Hydrolysis Lignin.Nanomaterials (Basel, Switzerland) · 2019Article
- Topoisomerases and cancer chemotherapy: recent advances and unanswered questions.F1000Research · 2019Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Contrary to other anticancer targets, topoisomerase I (TOP1) is targeted by only one chemical class of FDA-approved drugs: topotecan and irinotecan, the derivatives of the plant alkaloid, camptothecin. The indenoisoquinolines LMP400, LMP744, and LMP776 are novel noncamptothecin TOP1 inhibitors in clinical trial, which overcome the limitations of camptothecins. To further improve metabolic stability, their methoxy groups have been replaced by fluorine, as in the fluoroindenoisoquinolines NSC 781517 (LMP517), NSC 779135 (LMP135), and NSC 779134 (LMP134). We tested the induction and stability of TOP1 cleavage complexes (TOP1cc), and the induction and persistence of DNA damage measured by histone H2AX phosphorylation (γH2AX) compared with their parent compounds LMP744 and LMP776 in leukemia CCRF-CEM and colon carcinoma HCT116 cells. The fluoroindenoisoquinolines induced TOP1cc and γH2AX at nanomolar concentrations, and at higher levels than the parent indenoisoquinolines. The fluoroindenoisoquinoline LMP135 showed greater antitumor activity than topotecan in small-cell lung cancer cell H82 xenografts. It was also more potent than topotecan in the NCI-60 cancer cell line panel. Bioinformatics tools (http://discover.nci.nih.gov/cellminercdb) were used to investigate the following: (i) the correlations of fluoroindenoisoquinolines activity with other drugs, and (ii) genomic determinants of response in the NCI-60. The activity of the fluoroindenoisoquinolines was mostly correlated with camptothecin derivatives and the parent indenoisoquinolines, consistent with TOP1 targeting. Genomic analyses and activity assays in CCRF-CEM
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Registered trials
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