Rapamycin and CCI-779

Rapamycin (sirolimus) is a macrolide, related to cyclosporine with immunosu ppressive properties and antiproliferative activity in various human tumor cells lines and tumor xenograft models. The cytosolic kinase mTOR which con trols 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 asymptoma tic thrombopenia and hyperlipemia were observed. In murine models, best ant itumoral activity was observed using parental routes. CCI-779, an analog fo rmulated for intravenous use has antitumor activity without significant imm unosuppressive property in mice and is currently in phase I trials in man.