OF4949, new inhibitors of aminopeptidase B. IV. Effects of OF4949 and its derivatives on enzyme systems.
OF4949-I and II inhibited aminopeptidase B from Ehrlich ascites carcinoma in a competitive way and the Ki value for both against L-arginine-beta-naphthylamide was 8 X 10(-9) M. Inhibition by I and II of various exopeptidases and endopeptidases was examined. OF4949-I and II both strongly inhibited leucine aminopeptidase and enkephalin-degrading aminopeptidase; I also inhibited enkephalinase B. The inhibitory effects of various derivatives of I and II on aminopeptidase B activity, showed that the terminal amino and carboxamide groups are essential for activity.
D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D005260:Female; D007942:Leukemia, Experimental / Q000201:enzymology*; D008099:Liver / Q000201:enzymology; D008214:Lymphocytes / Q000201:enzymology; D008264:Macrophages / Q000201:enzymology; D051379:Mice; D008811:Mice, Inbred DBA; D008813:Mice, Inbred ICR; D008815:Mice, Inbred Strains; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D012510:Sarcoma 180 / Q000201:enzymology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D000903:Antibiotics, Antineoplastic; D010456:Peptides, Cyclic; D011480:Protease Inhibitors; C051497:OF 4949-II; C051496:OF 4949-I; C051701:OF 4949-F; C051700:OF 4949-D; D000626:Aminopeptidases; C019721:aminopeptidase B