Org 33201: a new highly selective orally active aromatase inhibitor.
Org 33201 has been selected as a very potent aromatase inhibitor. The compound is an enantiomer of a SC2H5 substituted imidazoylethylphenalene. Org 33201 inhibited human aromatase activity for 50% at a concentration of 2.2 x 10(9) mol/l. More than 200-fold higher concentrations were needed for the inhibition of other cytochrome P-450 enzymes. In vivo the compound was active in rats (ED50 = 0.035 mg/kg) and dogs (1 mg/kg gave 70% inhibition) after oral administration. It can be concluded that Org 33201 is a potent and highly selective orally active aromatase inhibitor.
Geelen
J A
JA
Scientific Development Group, Organon Int., Oss, The Netherlands.
Loozen
H J
HJ
Deckers
G H
GH
de Leeuw
R
R
Kloosterboer
H J
HJ
Lamberts
S W
SW
D000284:Administration, Oral; D000818:Animals; D047072:Aromatase Inhibitors; D002417:Cattle; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000037:antagonists & inhibitors; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D005260:Female; D006801:Humans; D007016:Hypophysectomy; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D043803:Phenalenes; D011083:Polycyclic Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D013739:Testosterone / Q000378:metabolism; D014621:Vagina / Q000187:drug effects* / Q000473:pathology
D047072:Aromatase Inhibitors; D006063:Chorionic Gonadotropin; D007093:Imidazoles; D043803:Phenalenes; D011083:Polycyclic Compounds; C080905:Org 33201; D013739:Testosterone; D003687:Dehydroepiandrosterone; D002786:Cholesterol Side-Chain Cleavage Enzyme