[Development of new hypoxic cell radiosensitizer in Japan].
Basic studies in hypoxic cell radiosensitizers developed in Japan were reviewed. Because of the unsuccessful clinical trials of misonidazole (MISO), many efforts have been made to find a new hypoxic cell sensitizer which is more effective and/or less toxic than MISO. Already over a thousand drugs were tested, but the majority of them did not work in vivo or were very toxic to the animals. Finally four drugs, KU-2285, KIH-801 (802), RK-28 and RP-170, have been proven to be effective both in vitro and in vivo. All of them are derivatives of 2-nitroimidazole. The first two have different side chains of fluorinated amide and acetohydroxamic acid, respectively. The second two both have sugar moieties. Investigations are now under way to find possible clinical applicability.
Mori
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T
Dept. of Radiation Oncology, School of Med. Tokai Univ.
Murayama
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C
D000818:Animals; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D017341:Etanidazole; D006877:Hydroxamic Acids / Q000493:pharmacokinetics / Q000627:therapeutic use; D051379:Mice; D008920:Misonidazole / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D009593:Nitroimidazoles / Q000493:pharmacokinetics / Q000627:therapeutic use; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use
D006877:Hydroxamic Acids; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; C047778:1-(4'-hydroxy-2'-butenoxy)methyl-2-nitroimidazole; C057685:2-nitroimidazole-1-acetohydroxamic acid; D017341:Etanidazole; D008920:Misonidazole