Experimental antitumor activity of BMY-28090, a new antitumor antibiotic.

Abstract

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)