RU54115, a tight-binding aromatase inhibitor potentially useful for the treatment of breast cancer.
RU54115 is a new potent inhibitor of aromatase. In vitro, it inhibits the enzyme from human placental microsomes with a Ki of 0.5 nM, which places it among the tightest reported steroidal inhibitors of aromatase. In vivo, it lowers the amount of circulating estradiol in pregnant mare serum gonadotrophin (PMSG)-primed female rats with an ED50 of 0.4 mg/kg when given s.c. and 4 mg/kg when given orally. An oral dose of 25 mg/kg when given once daily to female rats was able to inhibit the growth of DMBA-induced mammary tumors.
Delaisi
C
C
Centre de Recherches de Roussel-Uclaf, Romainville, France.
Doucet
B
B
Hartmann
C
C
Tric
B
B
Gourvest
J F
JF
Lesuisse
D
D
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000188:drug therapy; D004958:Estradiol / Q000097:blood*; D004963:Estrenes / Q000494:pharmacology* / Q000627:therapeutic use; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D006064:Gonadotropins, Equine / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D008861:Microsomes / Q000201:enzymology; D015394:Molecular Structure; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains
D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D004963:Estrenes; D004965:Estrogen Antagonists; D006064:Gonadotropins, Equine; C074095:10-methylthioethyl estra-4,9(11)-diene 3,17-dione; D004958:Estradiol; D015127:9,10-Dimethyl-1,2-benzanthracene