Testing of the topoisomerase 1 inhibitor Genz-644282 by the pediatric preclinical testing program

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Preclinical Development Molecular and Cellular Pharmacology of the Novel Noncamptothecin Topoisomerase I Inhibitor Genz-644282

Camptothecin derivatives are powerful anticancer drugs because of their ability to trap topoisomerase I (Top1)–DNA cleavage complexes. However, they exhibit clinical limitations due to the instability of their a-hydroxylactone six-membered E-ring structure. In addition, they exhibit bone marrow and intestinal toxicity, especially in adults, and are drug efflux substrates. Here, we report a nove...

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Molecular and cellular pharmacology of the novel noncamptothecin topoisomerase I inhibitor Genz-644282.

Camptothecin derivatives are powerful anticancer drugs because of their ability to trap topoisomerase I (Top1)-DNA cleavage complexes. However, they exhibit clinical limitations due to the instability of their α-hydroxylactone six-membered E-ring structure. In addition, they exhibit bone marrow and intestinal toxicity, especially in adults, and are drug efflux substrates. Here, we report a nove...

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Pediatric Preclinical Testing Program (PPTP) – May 2012

In vitro testing: In vitro testing was performed using DIMSCAN, a semiautomatic fluorescencebased digital image microscopy system that quantifies viable (using fluorescein diacetate [FDA]) cell numbers in tissue culture multiwell plates [1]. Cells were incubated in the presence of drug for 96 hours. Mean fluorescence values were determined for each concentration tested and then normalized to th...

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Genz-644282, a novel non-camptothecin topoisomerase I inhibitor for cancer treatment.

PURPOSE Genz-644282 [8,9-dimethoxy-5-(2-N-methylaminoethyl)-2,3-methylenedioxy-5H-dibenzo[c,h][1,6]naphthyridin-6-one] has emerged as a promising candidate for antitumor agents. This report describes the bone marrow colony-forming unit, granulocyte macrophage (CFU-GM) and tumor cell CFU activity of topoisomerase I (Top1) inhibitors, such as Genz-644282, topotecan, irinotecan/SN-38, and ARC-111,...

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Stage 2 combination testing of rapamycin with cytotoxic agents by the Pediatric Preclinical Testing Program.

Rapamycin demonstrated broad-spectrum tumor growth inhibition activity against the in vivo panels of childhood tumors used in the Pediatric Preclinical Testing Program (PPTP). Here we have evaluated rapamycin combined with agents used frequently in the treatment of childhood malignancies. Rapamycin was tested in vitro against 23 cell lines alone or in combination with melphalan, cisplatin, vinc...

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ژورنال

عنوان ژورنال: Pediatric Blood & Cancer

سال: 2011

ISSN: 1545-5009

DOI: 10.1002/pbc.23016