New synthetic inhibitor to the alternative complement pathway.
The inhibitory effects of 6-amidino-2-naphthyl 4-guanidinobenzoate (FUT-175) on the activities of factor B, factor D and cobra venom factor (CVF) X Bb were examined. FUT-175 bound specifically to the Bb fragment of factor B or CVF X Bb. FUT-175 was a non-competitive inhibitor of the esterolysis of L-leucyl-L-alanyl-L-arginine naphthylester by factor B and CVF X Bb. FUT-175 also inhibited the haemolytic activity of factor B, the C3 convertase activity of CVF X Bb and the factor B-cleaving activity of factor D. The concentration of FUT-175 causing 50% inhibition of these activities was 10(-5) - 10(-4)M.
D000818:Animals; D001550:Benzamidines; D003167:Complement Activation / Q000187:drug effects*; D011415:Complement Factor B / Q000037:antagonists & inhibitors; D011416:Complement Factor D / Q000037:antagonists & inhibitors; D003169:Complement Inactivator Proteins / Q000494:pharmacology*; D003170:Complement Pathway, Alternative / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004546:Elapid Venoms / Q000037:antagonists & inhibitors; D004591:Electrophoresis, Polyacrylamide Gel; D006146:Guanidines / Q000494:pharmacology*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D011817:Rabbits
D001550:Benzamidines; D003169:Complement Inactivator Proteins; D004546:Elapid Venoms; D006146:Guanidines; C016310:cobra venom factor; C493488:CFD protein, human; D011416:Complement Factor D; D011415:Complement Factor B; C032855:nafamostat