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Month: March 2011

TopoGEN Activity Assays: Topo II Inhibitor Study

TopoGEN Activity Assays: Topo II Inhibitor Study

Thanatop: A Novel 5-Nitrofuran that Is a Highly Active, Cell-Permeable Inhibitor of Topoisomerase II Abstract A series of nitrofuran-based compounds were identified as inhibitors of estrogen signaling in a cell-based, high-throughput screen of a diverse library of small molecules. These highly related compounds were subsequently found to inhibit topoisomerase II in vitro at concentrations similar to that required for the inhibition of estrogen signaling in cells. The most potent nitrofuran discovered is f10-fold more active than etoposide phosphate, a topoisomerase…

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Gyrase B Inhibitor Potential HIV Treatment

Gyrase B Inhibitor Potential HIV Treatment

Gyrase B Inhibitor Impairs HIV-1 Replication by Targeting Hsp90 and the Capsid Protein Chemical genetics is an emerging approach to investigate the biology of host-pathogen interactions. We screened several inhibitors of ATP-dependent DNA motors and detected the gyrase B inhibitor coumermycin A1 (C-A1) as a potent antiretroviral. C-A1 inhibited HIV-1 integration and gene expression from acutely infected cell, but the two activities mapped to distinct targets. Target discovery identified Hsp90 as the C-A1 target affecting viral gene expression. Chromatin immunoprecipitation…

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Topo I Assay Kit Aids Breast Cancer Study

Topo I Assay Kit Aids Breast Cancer Study

Epidermal Growth Factor-Induced Heparanase Nucleolar Localization Augments DNA Topoisomerase I Activity in Brain Metastatic Breast Cancer Abstract Identification of molecular mechanisms responsible for brain metastatic breast cancer (BMBC) is imperative to develop novel therapies. However, current understanding of the molecular circuitry that governs BMBC dissemination remains fragmentary. Heparanase (HPSE) is the only functional mammalian endoglycosidase whose activity correlates with cancer metastasis, angiogenesis, and the reduced postoperative survival of cancer patients, making it an active target for anticancer therapeutics. We hypothesized…

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DNA Cleavage Assay Aids The Clinical Search for New Top1 Inhibitors

DNA Cleavage Assay Aids The Clinical Search for New Top1 Inhibitors

DNA cleavage assay for the identification of topoisomerase I inhibitors The inhibition of DNA topoisomerase I (Top1) has proven to be a successful approach in the design of anticancer agents. However, despite the clinical successes of the camptothecin derivatives, a significant need for less toxic and more chemically stable Top1 inhibitors still persists. Here, we describe one of the most frequently used protocols to identify novel Top1 inhibitors. These methods use uniquely 3′-radiolabeled DNA substrates and denaturing polyacrylamide gel electrophoresis…

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