Cortexolone 17α-propionate (Clascoterone) Is a Novel Androgen Receptor Antagonist that Inhibits Production of Lipids and Inflammatory Cytokines from Sebocytes In Vitro

Abstract

Cortexolone 17α-propionate (clascoterone) is a novel topical androgen antagonist that is being analyzed for its ability to treat acne. The pathogenesis of acne is attributed to multiple factors, including altered sebum production, inflammatory processes, dysregulation of the hormone microenvironment, and the proliferation of the skin commensal bacteria, Propionibacterium acnes (P. acnes). Androgens induce the proliferation and differentiation of sebocytes, (cells that comprise the sebaceous gland), help regulate the synthesis of the lipids that are incorporated into sebum and stimulate the production of cytokines that are found in inflammatory acne lesions. Several studies have established that clascoterone is a potent antiandrogen that is well tolerated and has selective topical activity. Its potency as an acne therapeutic is currently being analyzed in a large phase 3 clinical trial. The study described herein elucidates for the first time the mechanism of action of clascoterone. Clascoterone was found to bind the androgen receptor (AR) with high affinity in vitro, inhibit AR-regulated transcription in a reporter cell line, and antagonize androgen-regulated lipid and inflammatory cytokine production in a dose-dependent manner in human primary sebocytes. In particular, when compared to another AR antagonist, spironolactone, clascoterone was significantly better at inhibiting inflammatory cytokine synthesis from sebocytes. Therefore, clascoterone may be an excellent candidate to be the first topical antiandrogen to treat acne. J Drugs Dermatol. 2019;18(5):412-418.

• Authors: Caridad Rosette, Frances J. Agan, Alessandro Mazzetti, Luigi Moro, Mara Gerloni
• Journal: Journal of drugs in dermatology : JDD (J Drugs Dermatol) Vol. 18 Issue 5 Pg. 412-418 (May 01 2019) ISSN: 1545-9616 [Print] United States
• PMID: 31141847 (Publication Type: Journal Article)

Chemical References

• Androgen Receptor Antagonists
• Cytokines
• Propionates
• Receptors, Androgen
• Cortodoxone
• Clascoterone

Topics

• Acne Vulgaris (drug therapy, microbiology)
• Androgen Receptor Antagonists (pharmacology, therapeutic use)
• Cell Line (drug effects)
• Cortodoxone (analogs & derivatives, pharmacology, therapeutic use)
• Cytokines (metabolism)
• Humans
• Lipogenesis (drug effects)
• Propionates (pharmacology, therapeutic use)
• Propionibacterium acnes
• Receptors, Androgen (metabolism)
• Sebaceous Glands (cytology, drug effects, metabolism)