ArticleProceedings of the National Academy of Sciences of the United States of America2023
Identification and characterization of topoisomerase III beta poisons.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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The trial behind it
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- Genome-wide mapping reveals increased R-loops in topoisomerase III-beta-deficient human cells.iScience · 2026Article
- MeCP2 NID interaction with RNA: implications for Rett syndrome-relevant protein regulation.Human molecular genetics · 2026Article
- Selective Isolation of TOP3B•mRNA Covalent Intermediates Using Denaturing Oligo-dT Pulldown.Bio-protocol · 2026Article
- Search for Specific Inhibitors Targeting Type IA Topoisomerases.Journal of molecular biology · 2026Review
- The Roles of Topoisomerases in Transcriptional Regulation.International journal of molecular sciences · 2026Review
- Decoding the lncRNA World: Comprehensive Approaches to lncRNA Structure and Interactome Studies.Cells · 2026Review
- An autism spectrum disorder mutation in Topoisomerase 3β causes accumulation of covalent mRNA intermediates by disrupting metal binding within the zinc finger domain.Nucleic acids research · 2025Article
- An autism spectrum disorder mutation in Topoisomerase 3β causes accumulation of covalent mRNA intermediates by disrupting metal binding within the zinc finger domain.bioRxiv : the preprint server for biology · 2025Article
- Furanoheliangolides fromJournal of natural products · 2025Article
- Substituted Triazole-3,5-Diamine Compounds as Novel Human Topoisomerase III Beta Inhibitors.International journal of molecular sciences · 2025Article
- The TDRD3-USP9X complex and MIB1 regulate TOP3B homeostasis and prevent deleterious TOP3B cleavage complexes.Nature communications · 2023Article
- Unraveling the Role of Topoisomerase 3β (TOP3B) in mRNA Translation and Human Disease.Wiley interdisciplinary reviews. RNAReview
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
We designed and carried out a high-throughput screen for compounds that trap topoisomerase III beta (TOP3B poisons) by developing a Comparative Cellular Cytotoxicity Screen. We found a bisacridine compound NSC690634 and a thiacyanine compound NSC96932 that preferentially sensitize cell lines expressing TOP3B, indicating that they target TOP3B. These compounds trap TOP3B cleavage complex (TOP3Bcc) in cells and in vitro and predominately act on RNA, leading to high levels of RNA-TOP3Bccs. NSC690634 also leads to enhanced R-loops in a TOP3B-dependent manner. Preliminary structural activity studies show that the lengths of linkers between the two aromatic moieties in each compound are critical; altering the linker length completely abolishes the trapping of TOP3Bccs. Both of our lead compounds share a similar structural motif, which can serve as a base for further modification. They may also serve in anticancer, antiviral, and/or basic research applications.
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Registered trials
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