[Rapamycin and CCI-779].
Rapamycin (sirolimus) is a macrolide, related to cyclosporine with immunosuppressive properties and antiproliferative activity in various human tumor cells lines and tumor xenograft models. The cytosolic kinase mTOR which controls the initiation of the translation of messenger RNA is the main known target of rapamycin. During clinical studies, rapamycin given by oral route as immunosuppressant did not show dose-limited toxicity and only asymptomatic thrombopenia and hyperlipemia were observed. In murine models, best antitumoral activity was observed using parental routes. CCI-779, an analog formulated for intravenous use has antitumor activity without significant immunosuppressive property in mice and is currently in phase I trials in man.
Alexandre
J
J
Département de médecine, Institut Gustave-Roussy, 94805 Villejuif Cedex.
Raymond
E
E
Armand
J P
JP
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D004195:Disease Models, Animal; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D007275:Injections, Intravenous; D051379:Mice; D009368:Neoplasm Transplantation; D014176:Protein Biosynthesis / Q000187:drug effects; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger / Q000187:drug effects; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D007166:Immunosuppressive Agents; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; C401859:temsirolimus; D020123:Sirolimus