BMY-28175 is a novel antitumor
antibiotic produced in fermentation by Actinomadura verrucosospora. The cytotoxic effects of
BMY-28175 were determined using murine and human tumor cell lines in vitro. Following 72 hour exposure, the
drug had IC50 values 1.5 to 13.5 ng/ml in a microtiter assay.
BMY-28175 was evaluated for antitumor activity against several experimental murine and human
tumor models. The
drug administered ip was active against ip implanted
P388 leukemia,
L1210 leukemia,
B16 melanoma, M109 lung
carcinoma, C26 colon
carcinoma, M5076
sarcoma and
Lewis lung carcinoma. In addition,
BMY-28175 administered iv was active against iv implanted P388 and L1210
leukemias.
BMY-28175 was active against sc implanted
B16 melanoma (increased lifespan and/or inhibition of primary
tumor growth) in about 60% of the tests. The growth of sc implanted M109 was inhibited by
BMY-28175 in a single experiment.
BMY-28175 was also active against the MX-1 human mammary xenograft implanted in the subrenal
capsule of nude mice. The optimal dose for
BMY-28175 in these various studies ranged from 0.16 micrograms/kg per injection with consecutive daily (qd1-9) administration, to 51.2 micrograms/kg with single dose administration. The results of these studies indicate that
BMY-28175 is one of the most potent
antitumor agents yet observed, with a broad spectrum of activity against
tumors of murine and human origin and activity against
tumors located distal to the site of
drug administration.