S160202

S-16020-2 (20) is a derivative of the olivacine class of pyridocarbazoles,115 containing a (dimethylamino)ethylcarbox-amide side chain that confers tight DNA intercalative binding properties. The drug is a potent stimulator of topo II-mediated DNA cleavage.116 It appears to be little affected by P-gp-mediated multidrug resistance, both in cell lines in culture,117 and in vivo.118 S-16020-2 was superior to doxorubicin in 5/13 human tumor xenografts in mice

(NCI-H460, A549, NCI-H69, SCLC6, and NIH:OVCAR-3) in terms of growth delay when given on a weekly schedule.119 It was superior to doxorubicin and cyclophosphamide against chemoresistant A549 nonsmall cell lung carcinomas in nude mice, A549 tumor cells metastases in severe combined immunodeficiency (SCID) mice, and intravenously implanted Lewis lung carcinomas.120 Preliminary conference reports of Phase I trials suggest a maximum tolerated dose of about 150 mgm _ 2, with the major toxicity being acne-like lesions.

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