The mechanism of Amifostine (WR-2721) mediated radioprotection is poorly understood. The effects of amifostine on human basal metabolism, mouse liver metabolism and on normal and tumor hepatic cells were studied. Indirect calorimetric canopy tests showed significant reductions in oxygen consumption and of carbon dioxide emission in cancer patients receiving amifostine. Glucose levels significan...

CC-1065 is a potent antitumor antibiotic which is cytotoxic to P388 and L1210 leukemia cells in vitro and in vivo. CC-1065 covalently binds to calf thymus DNA preferentially to adenine-thymine regions at N3 of adenine. Here, we compare CC-1065 interaction with P388-derived chromatin, DNA, and histones as measured by electronic absorption and circular dichroism. Two CC-1065 analogues (U-71,184 a...

Amifostine (S-2±3-aminopropylaminoethyl phosphorothioic acid), also known as WR-2721, is an aminothiol developed during the 1950s by the U.S. Army as a radio-protective agent (Murray, 1998). Amifostine is dephosphorylated in vivo to the active metabolite WR-1065, which enters cells by passive diffusion (Mitchell et al, 1995) and acts as a potent scavenger of free radicals and inhibitor of DNA d...

CC-1065 (NSC 298223), a potent new antitumor antibiotic produced by Streptomyces zelensis, interacts strongly with double-stranded DNA and appears to exert its cytotoxic effects through disruption of DNA synthesis. We undertook this study to elucidate the sites and mechanisms of CC-1065 interaction with DNA. The binding of CC-1065 to synthetic and native DNA was examined by differential circula...

CC-1065 is a potent antitumor antibiotic produced by Streptomyces zelensis. The drug binds covalently through N-3 of adenine and lies within the minor groove of DNA. Previous studies indicated that CC-1065 reacted with adenine in DNA to yield a thermally labile product that could be used to reveal its sequence specificity. These studies also provided insight into a DNA sequence (5'-CGGAGTTAGGGG...

The structure of CC-1065 (Fig. 1) was determined by X-ray crystallography5,6). Prior to isolation of a suitable crystalline form of CC-1065 for X-ray diffraction data collection, a chemical degradation product (1) obtained by reaction of CC-1065 with ethyl isocyanate in pyridine was crystallized and its structure determined by X-ray crystallography". A closely related compound, PDE I (2), was p...