Contract R&D to Identify Drugs that Target Human Topo I, Topo II, Bacterial Topo IV and DNA Gyrase

Contract Screening Services Experience. Rapid Turn-Around. Publication Quality. TopoGEN has >20 yrs. experience in the area as a Contract Research Organization and we stand behind our results. We guarantee clear, cosmetic data and unambiguous interpretations. You will receive a publication quality product. We are seasoned veterans in the arena of in vitro testing. More importantly, […]

The use of topoisomerase I inhibitors in multiple myeloma.

The standard treatment of multiple myeloma is systemic chemotherapy. Despite 30 years of drug development in myeloma, there are no new drug regimens significantly superior to melphalan and prednisone. In addition, phase II studies of new drugs in myeloma have been disappointing, with low response rates and no prolongation in survival. The topoisomerase I (topo […]

Topoisomerase I inhibitors: review and update.

This review presents a summary of preclinical and clinical data on the topoisomerase I (topo I) inhibitors that are under clinical development. To date, all of the topo I inhibitors that have been clinically evaluated are analogues of camptothecin, an extract of the Chinese tree Camptotheca acuminata. The therapeutic development of camptothecin was initially limited […]

DNA topoisomerase II rescue by catalytic inhibitors: a new strategy to improve the antitumor selectivity of etoposide.

The nuclear enzyme DNA topoisomerase II (topo II) is the target of important antitumor agents such as etoposide. Recent work has classified topo II targeting drugs into either topo II poisons that act by stabilizing enzyme-DNA cleavable complexes leading to DNA breaks, or topo II catalytic inhibitors that act at stages in the catalytic cycle […]

Anthracycline drug targeting: cytoplasmic versus nuclear–a fork in the road.

The anthracycline antibiotics doxorubicin (Adriamycin; DOX) and daunorubicin (DNR) continue to be essential components of first-line chemotherapy in the treatment of a variety of solid and hematopoietic tumors. The overall efficacies of DOX and DNR are, however, impeded by serious dose-limiting toxicities, including cardiotoxicity, and the selection of multiple mechanisms of cellular drug resistance. These […]

Mechanism of action of camptothecin.

Camptothecin (CPT) class of compounds has been demonstrated to be effective against a broad spectrum of tumors. Their molecular target has been firmly established to be human DNA topoisomerase I (topo I). CPT inhibits topo I by blocking the rejoining step of the cleavage/religation reaction of topo-I, resulting in accumulation of a covalent reaction intermediate, […]

Dual topoisomerase I/II inhibitors in cancer therapy.

While the majority of topoisomerase (topo) inhibitors show selectivity against either topo I or topo II, a small class of compounds can act against both enzymes. These can be divided into three classes. The first and largest class comprise drugs that bind to DNA by intercalation and include the clinically-evaluated acridine DACA, the benzopyridoindole intoplicine, […]

Biological targets of antitumor indolocarbazoles bearing a sugar moiety..

Natural and synthetic indolocarbazole compounds have triggered considerable interest since the discovery in 1986 of the inhibitory properties of staurosporine toward protein kinase C (PKC). Later, it has been shown that indolocarbazole compounds may inhibit various kinases, such as cyclin dependent-kinases and/or topoisomerase I, someones behave only as DNA intercalators. In this review are presented […]

The Impact of tumor physiology on camptothecin-based drug development

The genomic era has shifted anticancer drug development from its traditional mode concentrated on natural product cytotoxic agents to mechanism-based drug design focused on signal transduction pathways. Yet traditional cytotoxic chemotherapies continue to have an important role in the armamentarium. This is particularly true when one considers that important elements of solid tumor physiology – […]

CELL CONTEXT DNA REPAIR KITS NOW AVAILABLE

Cell Context DNA Repair Kits Are you working on DNA-damage and repair?  Would you be interested in a pre-validated cell-context system to analyze HR or NHEJ by single cell imaging or quantifying DNA repair by simple fluorescence? TopoGEN, Inc. has developed a suite of cell lines that will allow you to study specific DNA repair […]

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