KW-2149 2-[Y-L-GLUTAMYLAMINO]ETHYLDITHIOETHYL]MITOMYCIN-C) - A NEW MITOMYCIN-C ANALOG ACTIVATED BY SERUM

KW-2149 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 ex tracellular metabolism in serum. The metabolising activity differs bet ween batches of serum and species of origin. Human serum had high acti vity (which resulted in a 150-fold enhancement of cytotoxicity), where as 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 b e replaced by glutathione. No anticancer drug has previously been desc ribed whose toxicity is mediated by metabolism in serum. Copyright (C) 1997 Elsevier Science Inc.