arphamenine-b and ubenimex

Topics: Adjuvants, Immunologic; Animals; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Biological Products; Chemical Phenomena; Chemistry; Drug Evaluation, Preclinical; Glycine; Guanidines; Infections; Lactones; Leucine; Mice; Neoplasms, Experimental; Oligopeptides; Peptides

Topics: Animals; Animals, Newborn; Captopril; Drug Synergism; Evoked Potentials; gamma-Aminobutyric Acid; Glutamates; Glutamic Acid; Guanidines; Hydroxamic Acids; In Vitro Techniques; Kinetics; Leucine; Nerve Fibers; Neurokinin A; Protease Inhibitors; Rats; Rats, Wistar; Spinal Cord; Spinal Nerve Roots; Substance P; Tetrodotoxin; Thiorphan

Topics: Anti-Bacterial Agents; Cell Differentiation; Cell Line; Enzyme Inhibitors; Glycine; Guanidines; Humans; Leucine; Leukemia, Myeloid, Acute; Oligopeptides; Peptides; Protease Inhibitors

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....

Topics: Adjuvants, Immunologic; Aminopeptidases; Animals; Antibiotics, Antineoplastic; Glycine; Guanidines; Humans; Leucine; Molecular Weight

A study was performed to elucidate the effects of low-molecular-weight enzyme inhibitors on enzyme networks in vivo. Seven compounds, including bestatin and its 5 derivatives and arphamenine B, were tested, with each of them being administered to mice at the dose of 200 micrograms/day for 8 consecutive days. The spectrum of enzymatic changes thus induced were extensive and were not simply explainable by the in vitro actions of each agent administered. Nevertheless, a multivariate study on the changes in enzyme networks showed some degree of interrelationship between the in vitro and in vivo actions of the agents under study. The present findings seem to certify that the direct enzyme-inhibiting effect motivates the extensive movement of enzyme networks in vivo, although the latter often seems rather paradoxical at a glance.

Topics: Aminopeptidases; Animals; Enzyme Inhibitors; Guanidines; Leucine; Male; Mice; Mice, Inbred ICR; Spleen; Structure-Activity Relationship