Biological Profile of Cortexolone 17a-Propionate (CB-03-01), a New Topical and Peripherally Selective Androgen Antagonist

Abstract

The aim of this study was to investigate the antiandrogenic activity of a new monoester of cortexolone, cortexolone 17alpha-propionate (CAS 19608-29-8, CB-03-01). Although the compound displayed a strong local antiandrogenic activity in hamster's flank organ test, it did not exhibit antiandrogenic activity in rats after subcutaneous injection, nor did it affect gonadotropins hypersecretion when injected to parabiotic rats. As topical antiandrogen, the steroid resulted about 4 times more active than progesterone (CAS 57-83-0) and, when compared to known antiandrogen standards, it was about 3 times more potent than flutamide (CAS 13311-84-7), about 2 times more effective than finasteride (CAS 98319-26-7) and approximately as active as cyproterone acetate (CAS 427-51-0). Its pharmacological activity seemed to be primarily related to its ability to antagonistically compete at androgen receptor level; nevertheless its primary pharmacological target needs to be further investigated. Its topical activity, along with the apparent absence of systemic effects, anticipates this compound to have the potential of representing a novel and safe therapeutic approach for androgen-dependent skin disorders.

Cortexolone 17α-propionate 1% cream, a new potent antiandrogen for topical treatment of acne vulgaris. A pilot randomized, double-blind comparative study vs. placebo and tretinoin 0·05% cream

“…CB‐03‐01 is a new potent steroidal antiandrogen, with additional anti‐inflammatory properties, which was demonstrated in animal models to act selectively at the skin level without systemic effects 4,5 …”

“…Cortexolone 17α‐propionate (CB‐03‐01; Cosmo S.p.A, Lainate, Italy) is a new steroidal antiandrogen endowed with strong topical antiandrogenic activity associated with mild anti‐inflammatory properties 4,5 . CB‐03‐01 competes at the human androgen‐receptor level 6 without inhibiting the skin 5α‐reductase 7 .…”

A review of diagnosis and treatment of acne in adult female patients

“…Cortexolone 17α-propionate is a steroidal antiandrogen agent that has strong antiandrogen activity and mild anti-inflammatory properties ( Celasco et al, 2004 ). Cortexolone 17α-propionate competitively inhibits endogenous androgen binding at the human androgen receptor level without inhibiting the skin 5α-reductase ( Celasco et al, 2004 , Trifu et al, 2011 ).…”

“…Cortexolone 17α-propionate is a steroidal antiandrogen agent that has strong antiandrogen activity and mild anti-inflammatory properties ( Celasco et al, 2004 ). Cortexolone 17α-propionate competitively inhibits endogenous androgen binding at the human androgen receptor level without inhibiting the skin 5α-reductase ( Celasco et al, 2004 , Trifu et al, 2011 ). The agent is quickly metabolized once it penetrates the epidermis and frees inactive cortexolone; therefore, cortexolone 17α-propionate does not have systemic antiandrogenic effects ( Trifu et al, 2011 ).…”

Perspectives in acne therapy: an analytical review (in Russian only)

“…Следует отметить, что системное действие и возможность применения данного препарата у женщин детородного возраста исследованы не были. Также известно, что местная антиандрогенная активность кортексолон-17α пропионата выше, чем у прогестерона, флутамида и финастерида [97]. В настоящий момент препарат проходит III фазу клинических испытаний.…”