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A new article published in the Journal of Drugs in Dermatology reported that cortexolone 17α-propionate (clascoterone) – a novel topical androgen antagonist, is being analyzed for its ability to treat acne.
The authors discussed that the pathogenesis of acne is attributed to multiple factors, including altered sebum production, inflammatory processes, dysregulation of hormone microenvironment and 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. A number of 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.
This article elucidated 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. Furthermore, when compared to another AR antagonist – spironolactone, clascoterone proved significantly better at inhibiting inflammatory cytokine synthesis from sebocytes.
Hence, it was inferred that clascoterone may be an excellent candidate of being the first topical antiandrogen to treat acne.
Source: Journal of Drugs in Dermatology 2019 May 1;18(5):412-418.