6-Methylenandrosta-1,4-diene-3,17-dione (FCE 24304): a new irreversible aromatase inhibitor.
FCE 24304 (6-methylenandrosta-1,4-diene-3,17-dione), a new irreversible aromatase inhibitor, has been identified and characterized in vitro and in vivo. The compound caused time-dependent inactivation of human placental aromatase with a t1/2 of 13.9 min and ki of 26 nM. When tested in PMSG-treated rats, ovarian aromatase activity was reduced 24 h after dosing by both the s.c. (ED50 1.8 mg/kg) and the oral (ED50 3.7 mg/kg) routes. No interference with 5 alpha-reductase activity nor any significant binding affinity for estrogen receptor was found. Slight binding affinity for the androgen receptor (RBA 0.2% of DHT) was observed.
Giudici
D
D
Farmitalia C. Erba, R.&D./Oncology, Nerviano (MI), Italy.
Ornati
G
G
Briatico
G
G
Buzzetti
F
F
Lombardi
P
P
di Salle
E
E
D000730:Androstadienes / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D047072:Aromatase Inhibitors; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008861:Microsomes / Q000201:enzymology; D010053:Ovary / Q000201:enzymology; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D011467:Prostate / Q000378:metabolism; D051381:Rats; D011944:Receptors, Androgen / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D014599:Uterus / Q000378:metabolism
D000730:Androstadienes; D047072:Aromatase Inhibitors; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; C056516:exemestane