Biochem/physiol Actions
Fadrozole is a nonsteroidal aromatase inhibitor. Fadrozole is a very potent and highly selective inhibitor of the aromatase enzyme system in vitro and estrogen biosynthesis in vivo. It inhibited the conversion of [4-14C]androstenedione to [4-14C]estrone by human placental microsomes in a competitive manner (Ki = 1.6 nM). At a substrate concentration 3-fold the Km, Fadrozole was 180 times more potent, as an inhibitor, than aminoglutethimide (Cat. No. A9657), exhibiting half-maximal inhibition at 1.7 nM as compared to 0.3 μM. In vivo, Fadrozole lowered ovarian estrogen synthesis by gonadotropin-primed, androstenedione treated, immature rats by 90% at a dose of 260 μg/kg (PO). In vivo, Fadrozole leads to sequelae of estrogen deprivation (e.g. regression of DMBA-induced mammary tumors) without causing adrenal hypertrophy in adult rats. It blocked aromatase by 50% in human breast cancer homogenates, live breast cancer cells, human placental microsomes, and porcine ovarian microsomes at concentrations of 0.008 to 0.02 μM. |
Biochem/physiol Actions
Fadrozole is a nonsteroidal aromatase inhibitor. Fadrozole is a very potent and highly selective inhibitor of the aromatase enzyme system in vitro and estrogen biosynthesis in vivo. It inhibited the conversion of [4-14C]androstenedione to [4-14C]estrone by human placental microsomes in a competitive manner (Ki = 1.6 nM). At a substrate concentration 3-fold the Km, Fadrozole was 180 times more potent, as an inhibitor, than aminoglutethimide (Cat. No. A9657), exhibiting half-maximal inhibition at 1.7 nM as compared to 0.3 μM. In vivo, Fadrozole lowered ovarian estrogen synthesis by gonadotropin-primed, androstenedione treated, immature rats by 90% at a dose of 260 μg/kg (PO). In vivo, Fadrozole leads to sequelae of estrogen deprivation (e.g. regression of DMBA-induced mammary tumors) without causing adrenal hypertrophy in adult rats. It blocked aromatase by 50% in human breast cancer homogenates, live breast cancer cells, human placental microsomes, and porcine ovarian microsomes at concentrations of 0.008 to 0.02 μM. |