Low molecular weight immunomodifiers produced by microorganisms

Umezawa initiated the study of low molecular weight enzyme inhibitors produced by microorganisms and discovered more than 50 inhibitors which had various pharmacological activities. An extensive search was begun for inhibitors of enzymes on cell surfaces. Bestatin, amastatin, arphamenine, forphenicine, ebelactone thus found bound to cells and enhanced immune responses. The immunity enhancing effects of bestatin, forphenicinol (a derivative of forphenicine) and arphamenine have been studied in detail. The effect of bestatin in suppressing relapses and prolonging the survival period of patients were confirmed by randomized clinical tests with leukemia, melanoma, etc....