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Low molecular weight immunomodifiers produced by microorganisms.

H Umezawa, M Ishizuka

    International Journal of Clinical Pharmacology, Therapy, and Toxicology
    |April 1, 1985
    PubMed
    Summary
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    Microorganisms produce low molecular weight enzyme inhibitors with pharmacological activities. Bestatin and related compounds were found to enhance immune responses, with bestatin showing efficacy in clinical trials for leukemia and melanoma.

    Area of Science:

    • Microbiology
    • Immunology
    • Pharmacology

    Background:

    • Research into low molecular weight enzyme inhibitors from microorganisms began with Umezawa.
    • Over 50 inhibitors with diverse pharmacological activities were discovered.
    • Focus shifted to identifying inhibitors of cell surface enzymes.

    Purpose of the Study:

    • To explore enzyme inhibitors produced by microorganisms.
    • To investigate compounds that bind to cells and enhance immune responses.
    • To detail the immunity-enhancing effects of specific compounds like bestatin.

    Main Methods:

    • Screening microorganisms for enzyme inhibitor production.
    • Identifying inhibitors that interact with cell surface enzymes.
    • Conducting detailed immunological studies on selected compounds.

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  • Performing randomized clinical trials to confirm therapeutic effects.

    • Main Results:

    • Discovery of over 50 enzyme inhibitors with pharmacological activities.
    • Identification of bestatin, amastatin, arphamenine, forphenicine, and ebelactone.
    • Demonstration that bestatin, forphenicinol, and arphamenine enhance immune responses.
    • Clinical validation of bestatin's ability to suppress relapses and prolong survival in leukemia and melanoma patients.

    Conclusions:

    • Microbial enzyme inhibitors represent a promising source of pharmacologically active compounds.
    • Certain inhibitors, notably bestatin, possess significant immunomodulatory properties.
    • Bestatin has demonstrated clinical utility in improving outcomes for cancer patients.