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R1128 B (1,3,6-trihydroxy-8-n-butylanthraquinone), a new antibiotic produced by Streptomyces sp. No. 1128, inhibited estrogen binding to its receptor. The IC50 value of R1128 B for partially purified rat uterine cytosol receptor was 1.2 x 10(-7) M. However, the IC50 value of R1128 B against androgen-receptor binding was about 50-fold greater than that against estrogen-receptor binding. R1128 B was a competitive inhibitor against estrogen-receptor binding. R1128 B inhibited the growth of estrogen-responsive human mammary adenocarcinoma MCF-7 cells in soft agar. This inhibition, however, was reversed when estradiol was added to the culture medium. R1128 B showed antitumor activities against MCF-7 both xenografted to nude mice and implanted in subrenal capsule of mice (SRC assay). The potency of R1128 B was about 8-fold lower than that of tamoxifen both in vitro and in vivo.

journal of antibiotics

R1128 substances, novel non-steroidal estrogen-receptor antagonists produced by a Streptomyces. III. Pharmacological properties and antitumor activities.