Experimental antitumor activity of BMY-28090, a new antitumor antibiotic.
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)
Schurig
J E
JE
Bristol-Myers Co., Inc., Pharmaceutical Research and Development Division, Wallingford, CT 06492.
Bradner
W T
WT
Basler
G A
GA
Rose
W C
WC
D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; C049904:elsamicin A