Bestatin, a small molecular weight
dipeptide, is a potent inhibitor of various
aminopeptidases as well as
LTA4 hydrolase. Various physiological functions of
Bestatin have been identified, viz.: (1) an immunomodifier for enhancing the proliferation of normal human bone marrow granulocyte-macrophage progenitor cells to form CFU-GM colonies;
Bestatin exerts a direct stimulating effect on lymphocytes via its fixation on the cell surface and an indirect effect on monocytes via
aminopeptidase B inhibition of
tuftsin catabolism; (2) an immunorestorator and curative or preventive agent for spontaneous
tumor;
Bestatin alone or its combination with chemicals can prolongate the disease-free interval and survival period in adult acute or chronic
leukemia, therefore, it was primarily marketed in 1987 in Japan as an anticancer
drug and servers as the only marketed inhibitor of
Aminopeptidase N (APN/CD13) to cure
leukemia to date; (3) a pan-hematopoietic stimulator and restorator;
Bestatin promotes granulocytopoiesis and thrombocytopoiesis in vitro and restores them in myelo-hypoplastic men; (4) an inhibitor of several natural
opioid peptides. Based on the knowledge that APN can cleave several bioactive
neuropeptides such as Met-enkaphalins, Leu-enkaphalins,
beta-Endorphin, and so on, the anti-
aminopeptidase action of
Bestatin also allows it to protect endopeptides against their catabolism, exhibiting
analgesic activity. Although many scientific studies and great accomplishments have been achieved in this field, a large amount of problems are unsolved. This article reviews the promising results obtained for future development of the
analgesic activity of
Bestatin that can be of vital interest in a number of severe and
chronic pain syndromes.