Inhibitory effect of FUT-175 on complement activation and its application for glomerulonephritis with hypocomplementemia

• Published in: Nihon Jinzo Gakkai shi Vol. 35; no. 4; pp. 393 - 397
• Main Authors: FUJITA, YOSHIRO, INOUE, ITARU, INAGI, REIKO, MIYATA, TOSHIO, SHINZATO, TAKAHIRO, SUGIYAMA, SATOSHI, MIYAMA, AKIO, MAEDA, KENJI
• Format: Journal Article
• Language: English
• Published: Japan Japanese Society of Nephrology 01.04.1993
• Subjects: Adult; Child; Complement Activation - drug effects; Complement Inactivator Proteins - therapeutic use; Complement System Proteins - metabolism; Depression, Chemical; Female; FUT-175, serine protease inhibitor, complement activation, glomerulonephritis, hypocomplementemia; Glomerulonephritis - blood; Glomerulonephritis - drug therapy; Guanidines - therapeutic use; Humans; Male; Middle Aged; Proteinuria - drug therapy
• ISSN: 0385-2385; 1884-0728
• DOI: 10.14842/jpnjnephrol1959.35.393

FUT-175 (6-amidino-2-naphthy1 p-guanidinobenzoate dimethane-sulphonate), a potent serine protease inhibitor, has been reported to inhibit complement activity in vitro, and especially the classical complement pathway effectively. In the present study, we examined the inhibitory effect of FUT-175 on the classical complement pathway components by hemolytic assay using purified human complement components. As a result, 50% inhibition of the C1 protease activity for classical C3 convertase formation and for C2 was obtained with 3.0×10-8 M and 7.0×10-8M of FUT-175, respectively. FUT-175 did not inhibit the C2 protease activity at all. We then administered FUT-175 to 5 glomerulonephritic patients with hypocomplementemia and proteinuria in order to assess the clinical effectiveness of this drug. When FUT-l75 was administered intravenously and continuously at a rate of 0.1 to 0.2mg/kg/hr for 2 weeks, the urinary protein excretion decreased significantly from 2.9±0.8 to 1.4±0.5g/day (P<0.025). In these patients, some of the serum complement markers (serum C3, C4 level and the hemolytic activity via the classical complement pathway (CH50)) were increased after FUT-175 administration. The above findings suggests that FUT-175 can exert beneficial effects on glomerulonephritis with hypocomplementemia by inhibiting complement activation.