Ubenimex (
Bestatin) was discovered by Umezawa et al. in 1976 from the culture broth of Streptomyces olivoreticuli.
Bestatin is a compound of low-molecular weight
peptide and inhibits
leucine aminopeptidase and
aminopeptidase B which localized in cell membrane.
Bestatin exhibited antitumor effect against murine syngeneic
tumors including mouse colon 26 and C1498
leukemia, and also it was active against
MNNG-induced rat
tumor by
oral administration. Combination treatment of mouse colon 26 with
bestatin and
mitomycin C,
5-FU or CDDP was effective for the
life prolongation of the treated mice compared to mono-
therapy alone.
Bestatin was found to exhibit the antitumor effect through T lymphocyte stimulation, macrophage activation and bone marrow stem cell stimulation were also observed by
bestatin treatment experimentally. Values of T cell subsets in
cancer patients recovered to the normal levels by
Bestatin treatment. Release of
Interleukin-1 and -2 was enhanced by
Bestatin treatment in vitro. In the phase I study, clinical optimal daily dose was estimated as 10-100 mg to give 2-3 times weekly or daily continuously. In the comparative clinical trials,
Bestatin was found to be effective for the prolongation of survival time of the patients with acute non-
lymphocytic leukemia after induction of complete remission in combination with
maintenance chemotherapy. Minimal side effects were noted.