Abstract |
The effect of ONO-3307 (4-sulfamoyl phenyl-4-guanidinobenzoate methanesulfonate), a new protease inhibitor, was studied on various proteases in vitro and in an experimental thrombosis model in vivo. ONO-3307 competitively inhibited trypsin, thrombin, plasma kallikrein, plasmin, pancreatic kallikrein and chymotrypsin; and their Ki values were 0.048 microM, 0.18 microM, 0.29 microM, 0.31 microM, 3.6 microM and 47 microM, respectively. In addition, ONO-3307 inhibited both elastase release from N-formyl- Met-Leu-Phe (fMLP)-stimulated leukocytes and tissue thromboplastin release from endotoxin-stimulated leukocytes. To examine the effects of ONO-3307 on disseminated intravascular coagulation ( DIC), we developed an experimental thrombosis model. ONO-3307 (10 mg/kg/hr) completely inhibited the deposition of radioactive fibrin in kidney and lung. Gabexate mesilate (50 mg/kg/hr) was also effective in this model, but the effect of nafamostat mesilate was unclear. These results indicate that ONO-3307 exhibits a wide range of inhibitory effects on various proteases, and ONO-3307 may be useful for the treatment of protease-mediated diseases such as thrombosis and DIC.
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Authors | S Matsuoka, M Futagami, H Ohno, K Imaki, T Okegawa, A Kawasaki |
Journal | Japanese journal of pharmacology
(Jpn J Pharmacol)
Vol. 51
Issue 4
Pg. 455-63
(Dec 1989)
ISSN: 0021-5198 [Print] Japan |
PMID | 2515329
(Publication Type: Journal Article)
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Chemical References |
- Benzamidines
- Endotoxins
- Fibrinolytic Agents
- Guanidines
- Indicators and Reagents
- Serine Proteinase Inhibitors
- Gabexate
- N-Formylmethionine Leucyl-Phenylalanine
- ONO 3307
- Thromboplastin
- Pancreatic Elastase
- nafamostat
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Topics |
- Animals
- Benzamidines
- Dialysis
- Endotoxins
(pharmacology)
- Fibrinolytic Agents
- Gabexate
- Guanidines
(pharmacology)
- Humans
- In Vitro Techniques
- Indicators and Reagents
- Kinetics
- Leukocytes
(drug effects, enzymology)
- Male
- N-Formylmethionine Leucyl-Phenylalanine
(pharmacology)
- Pancreatic Elastase
(metabolism)
- Rats
- Rats, Inbred Strains
- Serine Proteinase Inhibitors
- Thromboplastin
(metabolism)
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