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Month: June 2011

Custom Drug Screening Services

Custom Drug Screening Services

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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Novel Gold Compounds Potential Anti-cancer Therapies

Novel Gold Compounds Potential Anti-cancer Therapies

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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Topotecan and its Effects on Human Topoisomerase I

Topotecan and its Effects on Human Topoisomerase I

A very nice paper has been recently published in the free access journal PLoS One.  These investigators are starting to ask important structural questions about how Topotecan, a clinically useful topoisomerase I poison, interacts with the enzyme to create a stable complex.  The authors go on to examine the molecular details on DNA deformation with drug/specific residue contacts.  By focusing on the ternary complex between topo/topotecan/DNA they have gained key insight to our understanding of the dynamics of the process….

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Novel Targeting In Vivo based on DNA DS Breaks and Homologous Recombination

Novel Targeting In Vivo based on DNA DS Breaks and Homologous Recombination

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.

Monitor Drug Efficacy with the In Vivo Link Kit from TopoGEN

Monitor Drug Efficacy with the In Vivo Link Kit from TopoGEN

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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Topoisomerase II Drug Sensitivity May Be Individually Determined

Topoisomerase II Drug Sensitivity May Be Individually Determined

Effect of a Single Nucleotide Polymorphism in the Murine Double Minute 2 Promoter (SNP309) on the Sensitivity to Topoisomerase II-Targeting Drugs Abstract A single nucleotide polymorphism (SNP) SNP309 (T–>G) in the murine double minute 2 (MDM2) promoter creates a high-affinity Sp1 binding site and increases the expression of MDM2 mRNA and protein. Approximately 40% of the populations harbor at least one variant allele and 12% to 17% are homozygous G/G at codon 309. This MDM2 SNP increases susceptibility to cancer…

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Human Topoisomerase II and Transcription

Human Topoisomerase II and Transcription

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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Topo I Cleavage Complexes and Transcription

Topo I Cleavage Complexes and Transcription

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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