The rediscovery of DON (6-diazo-5-oxo-L-norleucine).

DON (6-diazo-5-oxo-L-norleucine) and azotomycin are glutamine antagonists that were tested in human malignancies in the 1950s. Azotomycin demonstrated significant activity in colorectal cancer. DON is probably the active form of azotomycin. Recent impressive results for both of these agents in human tumor xenografts (especially the CX-2 colon tumor) have stimulated renewed clinical interest in DON, the more readily available agent. DON mechanism of action, clinical pharmacology, previous clinical data, and current phase I studies are discussed.