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Drug-Target Interaction

Drug

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PubChem ID:11273
Structure:
Synonyms:
(8R,9S,10R,13S,14S)-4-hydroxy-10,13-dimethyl-2,6,7,8,9,11,12,14,15,16-deca
4-Androsten-4-ol-3,17-dione
4-Hydroxy-4-androstene-3,17-dione
4-Hydroxy-delta(sub 4)-androstenedione
4-Hydroxyandrost-4-ene-3,17-dione
4-hydroxyandrostene-3,17-dione
4-Hydroxyandrostenedione
4-OH-A
4-OHA
566-48-3
A5791_SIGMA
AC1L1X05
AC1Q6OIC
Ambap677
Androst-4-ene-3,17-dione, 4-hydroxy-
B, Aromatase inhibitor
BRN 1889793
C19H26O3
CCRIS 7483
CGP 32 349
CGP 32349
CGP-32349
CHEBI:317341
CHEMBL132530
D07260
F2552_SIGMA
Formestane
Formestane (INN)
Formestane [BAN:INN]
Formestane [INN:BAN]
Formestane, Lentaron(R), 17-dione, CGP-32349, NSC 282175
Formestane-Supplied by Selleck Chemicals
HMS2090I22
HMS2234J06
Lentaron
Lentaron (TN)
Lentaron Depot
LS-19455
MLS000028826
MLS001148070
MLS002153359
NCGC00164380-01
NCI60_002316
NSC 282175
NSC282175
S2208_Selleck
SaveCream
SMR000058722
ST51051229
ZINC03919580
ATC-Codes:

Target

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Uniprot ID:CP19A_RAT
Synonyms:
Aromatase
CYPXIX
Cytochrome P450 19A1
Estrogen synthetase
P-450AROM
EC-Numbers:1.14.14.1
Organism:Rat
Rattus norvegicus
PDB IDs:-

Binding Affinities:

Ki: Kd:Ic 50:Ec50/Ic50:
----

References:

8142297
Effect of aromatase inhibitors on estrogen 2-hydroxylase in rat liver.. H S Purba; E J King; P Richert; A S Bhatnagar (1994) The Journal of steroid biochemistry and molecular biology display abstract
The effect of aromatase inhibitors, 4-hydroxyandrostenedione, CGS 16949A and aminoglutethimide on the inhibition of estrogen 2-hydroxylase activity in rat liver microsomes in vitro and on its induction in vivo has been examined. Estrogen 2-hydroxylase was found to have over twice the affinity for estradiol compared to estrone. Using high pressure liquid chromatography and employing estradiol as a substrate, the IC50 values were 2.2, 98, 110 and 908 microM for the reference compound ketoconazole and the aromatase inhibitors, 4-hydroxyandrostenedione, CGS 16949A and aminoglutethimide, respectively. Similar IC50 values were obtained using estrone as a substrate and by a tritiated water method employing estradiol as a substrate. The Km value for estrogen 2-hydroxylase with estradiol as a substrate using a tritiated water method was 4.3 microM with a Vmax of 11.89 nmol/h/mg. Ketoconazole, CGS 16949A and aminoglutethimide exhibited non-competitive inhibition whereas 4-hydroxyandrostenedione appeared to be a competitive inhibitor of estrogen 2-hydroxylase. The Ki values were 2.6, 72, 114 and 958 microM for ketoconazole, 4-hydroxyandrostenedione, CGS 16949A and aminoglutethimide, respectively. All three aromatase inhibitors were weak inhibitors of estrogen 2-hydroxylase as compared to the reference drug, ketoconazole. Following treatment of rats with aminoglutethimide (40 mg/kg/day; i.p.; for 3 days), estrogen 2-hydroxylase activity was increased by 28 and 30% using estradiol and estrone as substrates, respectively. Following treatment of rats with CGS 16949A (2 mg/kg/day; p.o.; for 3 days), the corresponding increase in estrogen 2-hydroxylase activity was 48 and 44%. The results of this study indicate that the aromatase inhibitors, aminoglutethimide and CGS 16949A are only weak inhibitors of estrogen 2-hydroxylase activity in vitro and show no evidence of inhibition in vivo. On the contrary, there was some evidence to suggest that both aminoglutethimide and CGS 16949A induce estrogen metabolism following repeated administration. Therefore, aminoglutethimide and CGS 16949A may lower estrogen levels not only by primarily inhibiting their synthesis but also by inducing the metabolism of estrogens.