Abstract |
Cortexolone 17α-propionate ( clascoterone) is a novel androgen antagonist that is currently being analyzed in a large phase 2 clinical trial for the topical treatment of androgenetic alopecia (AGA). While the pathogenesis of AGA is still debated, the consensus is that AGA is an androgen-dependent hair disorder with strong genetic links, and that the testosterone metabolite, dihydrotestosterone (DHT), plays a causal role in its development. DHT binds to the androgen receptor (AR) in scalp dermal papilla cells (DPC) to induce AR-mediated transcription of genes that contribute to AGA in genetically predisposed individuals. Several studies have established that clascoterone is a potent antiandrogen that is well tolerated and has selective topical activity. The study described herein elucidates a potential mechanism of clascoterone in AGA. Clascoterone was found to inhibit AR-regulated transcription in a reporter cell line with similar efficacy to the 5α-reductase inhibitor, finasteride. More importantly, when compared with another direct AR antagonist, enzalutamide, clascoterone was significantly better at inhibiting IL-6 synthesis from DHT-stimulated primary cultures of human scalp DPC. Therefore, clascoterone may be an excellent candidate to be the first topical antiandrogen for treating AGA. J Drugs Dermatol. 2019;18(2):197-201.
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Authors | Caridad Rosette, Niccolette Rosette, Alessandro Mazzetti, Luigi Moro, Mara Gerloni |
Journal | Journal of drugs in dermatology : JDD
(J Drugs Dermatol)
Vol. 18
Issue 2
Pg. 197-201
(Feb 01 2019)
ISSN: 1545-9616 [Print] United States |
PMID | 30811143
(Publication Type: Journal Article)
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Chemical References |
- Androgen Receptor Antagonists
- Propionates
- Receptors, Androgen
- Cortodoxone
- Clascoterone
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Topics |
- Administration, Topical
- Alopecia
(drug therapy, metabolism)
- Androgen Receptor Antagonists
(pharmacology)
- Cell Line
- Cells, Cultured
- Cortodoxone
(analogs & derivatives, pharmacology)
- Hair Follicle
(drug effects, metabolism)
- Humans
- Propionates
(pharmacology)
- Receptors, Androgen
(metabolism)
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