Growth inhibition of mouse autochthonous skin cancer by oral administration of new serine protease inhibitor ONO-3403.
The orally active serine protease inhibitor ONO-3403 is an analog of FOY-3403 that has more potent protease-inhibitory activity. In the present study, oral administration of ONO-3403 was used to challenge 3-methylcholanthrene-induced carcinoma. This drug was administered 3 times daily for 9 weeks via a stomach tube at a dose of 10 mg/kg in a 1-ml volume in 6 mice harboring solid tumors. This protease inhibitor significantly inhibited tumor growth (p<0.001) and prolonged survival-time (p<0.01). These results indicated that oral administration of the potent serine protease inhibitor ONO-3403 has an antitumor effect on malignant tumors.
Ohkoshi
Motohiro
M
Department of Oral and Maxillo-Facial Surgery, Branch Hospital, Faculty of Medicine, The University of Tokyo, Japan.
Okuda
Satoru
S
D000284:Administration, Oral; D000501:Allylglycine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D001550:Benzamidines / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006131:Growth Inhibitors / Q000494:pharmacology; D051379:Mice; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology
D001550:Benzamidines; D006131:Growth Inhibitors; D015842:Serine Proteinase Inhibitors; C100807:ethyl N-allyl-N-(2-methyl-3-(4-(4-amidinophenoxycarbonyl)phenyl)propenoyl)aminoacetate methanesulfonate; D000501:Allylglycine