In addition to manufacturing, TopoGEN has quietly developed into a CRO powerhouse in recent years.  Utilizing our own regimes and expertise that comes with 30+ years of experience, we tailor-build a custom screening solution for your novel anti-cancer studies.  Specific targets include eukaryotic topoisomerases (topo I, topo II, topo III), prokaryotic topoisomerases (gyrase, topo IV) in E. Coli and S. Aureus, and recently we added DNA methyltransferase targets.  We are also developing a solid phase assay for topo I (provisional…

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TopoGEN is partnering with a prominent analytical chemist based in South Africa on the development of innovative anti-topo I and II targeting drugs based on synthetic structures containing gold.  Evidence demonstrates the combination of poisoning and catalytic inhibition of the DNA topoisomerase pathways.  Initial screens performed by NCI demonstrated efficacy in cancer and subsequent confirmation by TopoGEN is showing topoisomerase targeting.   Further studies are pending SBIR phase I review and the acquisition of patents filed in the U.S. and abroad….

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TopoGEN scientists are working on a novel screening kit that reports on the topo II mediated DNA damage.  The kit comes bundled with a HR repair reporter that TopoGEN scientist engineered using GFP inside cells that contain an ultra-high affinity site for topoisomerase II cleavages.  The quantitative GFP readout will allow in vivo screening for topo active and DNA damaging agents.  This kit is slated for release in 2012, so please contact us for more information.

TopoGEN has developed a kit to clearly demonstrate topo I and II poisoning in the context of the cell.  Use of the In Vivo Link Kit™ provides the researcher unambiguous evidence of drug efficacy within tumor cells. Frequently, when a new drug or compound is identified as a topo targeting agent, the investigator needs to ask basic questions about its entry into the cell.  For example, a positive in vitro hit may not translate into the context of a tumor…

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DNA topoisomerase IIa is required for RNA polymerase II transcription on chromatin templates Neelima Mondal & Jeffrey D. Parvin Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA Abstract In the nucleus of the cell, core RNA polymerase II (pol II) is associated with a large complex called the pol II holoenzyme (holo-pol)1,2. Transcription by core pol II in vitro on nucleosomal templates is repressed compared with that on templates of histone-free naked DNA3±5. We…

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Role for topoisomerase 1 in transcription-associated mutagenesis in yeast High levels of transcription in Saccharomyces cerevisiae are associated with increased genetic instability, which has been linked to DNA damage. Here, we describe a pGAL-CAN1 forward mutation assay for studying transcription-associated mutagenesis (TAM) in yeast. In a wild-type background with no alterations in DNA repair capacity, ≈50% of forward mutations that arise in the CAN1 gene under high-transcription conditions are deletions of 2–5 bp. Furthermore, the deletions characteristic of TAM localize…

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