title: Pharmacological profile of 9,11-dehydrocortexolone 17alpha-butyrate (CB-03-04), a new androgen antagonist with antigonadotropic activity.
abstract: A series of new cortexolone-related derivatives has been synthesized and investigated for potential anti-androgenic activity. Among the steroids evaluated, 9,11-dehydrocortexolone 17alpha-butyrate (CB-03-04) was the most promising one. The compound displayed a strong local antiandrogenic activity in hamster's flank organ test, and it was also found to be effective in the rat after subcutaneous injection. When compared to other well known androgen antagonists, the rank order of topical anti-androgenic activity in that test was: cyproterone acetate (CAS 427-51-0) > or = CB-03-04 > finasteride (CAS 98319-26-7) > flutamide (CAS 13311-84-7). In addition, the steroid had selective antigonadotropic activity, when injected into parabiotic rats, and was about as active as progesterone. The activity of CB-03-04 was ascribed mainly to its ability to compete with the stimulating effects of testosterone and dihydrotestosterone and, concurrently, to inhibit the gonadotropins hypersecretion. This bimodal mechanism of action could be predictive for the clinical usefulness of the steroid in the treatment of prostate cancer and benign prostate hypertrophy.
authors.affiliation: Cosmo S.p.A., Lainate, Italy. giuseppe.celasco@cosmospa.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Celasco
authors.forename: Luigi
authors.initials: L
authors.lastname: Moroa
authors.forename: Roberta
authors.initials: R
authors.lastname: Bozzella
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ferraboschi
authors.forename: Luisa
authors.initials: L
authors.lastname: Bartorelli
authors.forename: Roberto
authors.initials: R
authors.lastname: Di Marco
authors.forename: Cinzia
authors.initials: C
authors.lastname: Quattrocchi
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
mesh_terms: D045930:Anabolic Agents / Q000494:pharmacology; D000726:Androgen Antagonists / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D003350:Cortodoxone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D006224:Cricetinae; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism; D006062:Gonadotropins / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar; D012015:Reference Standards; D013256:Steroids / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: C507126:9,11-dehydrocortexolone 17-butyrate; D045930:Anabolic Agents; D000726:Androgen Antagonists; D005938:Glucocorticoids; D006062:Gonadotropins; D013256:Steroids; D003350:Cortodoxone