R1128 substances, novel non-steroidal estrogen-receptor antagonists produced by a Streptomyces. III. Pharmacological properties and antitumor activities.
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.
Hori
Y
Y
Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Ibaraki, Japan.
Abe
Y
Y
Nishimura
M
M
Goto
T
T
Okuhara
M
M
Kohsaka
M
M
D059002:Androgen Receptor Antagonists; D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors*
D059002:Androgen Receptor Antagonists; D000880:Anthraquinones; D000903:Antibiotics, Antineoplastic; D011960:Receptors, Estrogen; C082781:1,3,6-trihydroxy-8-n-propylanthraquinone; C082782:1,3,6-trihydroxy-8-n-butylanthraquinone; C082783:1,3,6-trihydroxy-8-(3-methylbutyl)anthraquinone; C082784:1,3,6-trihydroxy-8-n-pentylanthraquinone