BMY-28090 is a novel actinomycete fermentation derived
antitumor agent. The cytotoxic effect of
BMY-28090 was evaluated in two murine and eight human tumor cell lines in vitro. Following 72-hour exposures,
BMY-28090 was cytotoxic for all of these cell lines with IC50 values of less than 0.02 to 3.25 micrograms/ml.
BMY-28090 was evaluated for in vivo antitumor activity in a variety of experimental murine
tumor and human
tumor xenograft models. Initial testing against the murine
tumor models was performed using
BMY-28090 as the water insoluble free base whereas subsequent antitumor tests were performed using water soluble
lactate or
succinate salts.
BMY-28090 administered ip demonstrated good, reproducible antitumor activity against ip implanted
P388 leukemia,
L1210 leukemia,
B16 melanoma and M5076
sarcoma. The water soluble preparations of
BMY-28090 were active iv against sc implanted
B16 melanoma and M5076
sarcoma as well as subrenal
capsule (src) M5076
sarcoma; activity against src implanted B16 was marginal.
BMY-28090 lactate was also evaluated for activity against src implanted MX-1 human mammary
tumor xenografts in nude mice and the HCT116 human colon
tumor xenografts in immune-suppressed BDF1 mice. At maximum tolerated doses administered ip,
BMY-28090 was active against the MX-1 xenograft in two of three tests, causing greater than 90% inhibition of
tumor growth.
BMY-28090 administered iv at maximally tolerated doses had marginal activity against the HCT116 xenografts, producing 61% and 68% inhibition of
tumor growth in two tests. The results of these studies demonstrated that
BMY-28090 has a broad spectrum of in vitro cytotoxicity against both murine and human tumor cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)