Antitumor effects of IST-622, a novel synthetic derivative of chartreusin, against murine and human tumor lines following oral administration.
The antitumor effects of 6-O-(3-ethoxypropionyl)-3',4'-O-exo- benzylidenechartreusin (IST-622), a new synthetic derivative of chartreusin (CT), were investigated. Following oral administration, IST-622 showed marked antitumor effects against various mouse tumors such as P388 and L1210 leukemias, B16 melanoma, Lewis lung carcinoma, Colon 26 and Colon 38 adenocarcinomas, and M5076 reticulum-cell sarcoma. The best antitumor effects were obtained by five intermittent treatments given every 4 days. In addition, IST-622 showed a significant growth-inhibitory effect against two human tumor xenografts, a large-cell lung cancer (Lu-116) and a gastric adenocarcinoma (St-4), among the seven lines tested. IST-622, which was rapidly metabolized into 3',4'-O-exo-benzylidenechartreusin (A-132) and not into CT in vivo or in culture medium, exhibited remarkable growth-inhibitory activity against P388 leukemia in vitro, its 50% growth-inhibitory concentration (IC50) being over 20-fold lower than that of CT. IST-622 showed an in vivo antitumor effect superior to that of authentic A-132, possibly resulting from a higher absorption ratio of IST-622 through the gastrointestinal tract. IST-622 is now under clinical phase I study in Japan.
Tashiro
T
T
Cancer Chemotherapy Center, Japanse Foundation for Cancer Research, Tokyo.
Kon
K
K
Yamamoto
M
M
Yamada
N
N
Tsuruo
T
T
Tsukagoshi
S
S
D000284:Administration, Oral; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D001578:Benzopyrans / Q000008:administration & dosage / Q000494:pharmacology; D004334:Drug Administration Schedule; D004354:Drug Screening Assays, Antitumor; D006027:Glycosides / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D007941:Leukemia P388 / Q000188:drug therapy; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation
D000903:Antibiotics, Antineoplastic; D001578:Benzopyrans; D006027:Glycosides; C088370:6-O-(3-ethoxypropionyl)-3',4'-O-exo-benzylidenechartreusin