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KW-2149 (7-N-[2-[Y-L-glutamylamino]ethyldithioethyl]mitomycin C) - A new mitomycin C analogue activated by serum

Masters, JRW; Know, RJ; Hartley, JA; Kelland, LR; Hendriks, HR; Connors, T; (1997) KW-2149 (7-N-[2-[Y-L-glutamylamino]ethyldithioethyl]mitomycin C) - A new mitomycin C analogue activated by serum. BIOCHEM PHARMACOL , 53 (3) 279 - 285.

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Abstract

KW-2149 (7-N-[2-[Y-L-glutamylamino]ethyldithioethyl]mitomycin C) is a new mitomycin-C analogue in clinical trial. This study demonstrates that KW-2149, unlike mitomycin C, is activated to a cytotoxic species by extracellular metabolism in serum. The metabolising activity differs between batches of serum and species of origin. Human serum had high activity (which resulted in a 150-fold enhancement of cytotoxicity), whereas mouse serum had low activity. In the presence of serum, the rate of uptake of H-3-KW-2149 into cells increased by 8-fold and drug binding to DNA by 32-fold. The metabolising activity of serum can partially be replaced by glutathione. No anticancer drug has previously been described whose toxicity is mediated by metabolism in serum. Copyright (C) 1997 Elsevier Science Inc.

Type: Article
Title: KW-2149 (7-N-[2-[Y-L-glutamylamino]ethyldithioethyl]mitomycin C) - A new mitomycin C analogue activated by serum
Keywords: new anticancer agent, mitomycin C, intravesical chemotherapy, bladder cancer, serum factor, drug metabolism, ANTITUMOR-ACTIVITY, CELL-LINES, RESISTANT, INVITRO, MURINE
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
URI: http://discovery.ucl.ac.uk/id/eprint/109038
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