ArticleMolecular cancer therapeutics2014
Biochemical assays for the discovery of TDP1 inhibitors.
Article in Molecular cancer therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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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
12 citing papers in PubMed, 17 citations in OpenAlex.
- Tyrosyl-DNA phosphodiesterase 2 (Tdp2) repairs DNA-protein crosslinks and protects against double strand breaksFrontiers in cell and developmental biology · 2024Article
- 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
- Excision repair of topoisomerase DNA-protein crosslinks (TOP-DPC).DNA repair · 2020Review
- 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.Nucleic acids research · 2019Article
- PRMT5-mediated arginine methylation of TDP1 for the repair of topoisomerase I covalent complexes.Nucleic acids research · 2018Article
- Neutral Porphyrin Derivative Exerts Anticancer Activity by Targeting Cellular Topoisomerase I (Top1) and Promotes Apoptotic Cell Death without Stabilizing Top1-DNA Cleavage Complexes.Journal of medicinal chemistry · 2018Article
- Synthesis, anti-cancer screening and tyrosyl-DNA phosphodiesterase 1 (Tdp1) inhibition activity of novel piperidinyl sulfamides.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2018Article
- Overexpression screens identify conserved dosage chromosome instability genes in yeast and human cancer.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Abacavir, an anti-HIV-1 drug, targets TDP1-deficient adult T cell leukemia.Science advances · 2015Article
- Targeting bacterial topoisomerase I to meet the challenge of finding new antibiotics.Future medicinal chemistry · 2015Review
- Article
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 1 country.
Funding
Abstract
Drug screening against novel targets is warranted to generate biochemical probes and new therapeutic drug leads. TDP1 and TDP2 are two DNA repair enzymes that have yet to be successfully targeted. TDP1 repairs topoisomerase I-, alkylation-, and chain terminator-induced DNA damage, whereas TDP2 repairs topoisomerase II-induced DNA damage. Here, we report the quantitative high-throughput screening (qHTS) of the NIH Molecular Libraries Small Molecule Repository using recombinant human TDP1. We also developed a secondary screening method using a multiple loading gel-based assay where recombinant TDP1 is replaced by whole cell extract (WCE) from genetically engineered DT40 cells. While developing this assay, we determined the importance of buffer conditions for testing TDP1, and most notably the possible interference of phosphate-based buffers. The high specificity of endogenous TDP1 in WCE allowed the evaluation of a large number of hits with up to 600 samples analyzed per gel via multiple loadings. The increased stringency of the WCE assay eliminated a large fraction of the initial hits collected from the qHTS. Finally, inclusion of a TDP2 counter-screening assay allowed the identification of two novel series of selective TDP1 inhibitors.
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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.