Clascoterone

Clascoterone (cortexolone 17 α-propionate) is a new androgen receptor antagonist. It binds to androgen receptors with high affinity. By competing with androgens for the receptor, clascoterone blocks the androgen receptor signalling cascades that promote acne pathogenesis, such as sebaceous gland proliferation, excess sebum production and inflammatory pathways.

Acne is a multifactorial skin condition. It is marked by excess sebum production, epithelial hyperkeratinization, proliferation of the skin commensal bacteria, and inflammation. Testosterone and dihydrotestosterone (DHT) are the natural ligands, and they circulate in the body and are also made locally. They are causative factors in both males and females. When DHT binds, the DHT-androgen receptor complex dimerizes and moves into the nucleus. There it promotes the transcription of genes involved in acne pathogenesis, including proliferation and differentiation of sebocytes, excess sebum production, and inflammatory cytokine production. Clascoterone is a potent antagonist at androgen receptors (ARs) and competes with androgens for binding to the receptor. In this way it inhibits the downstream signalling of ARs that promotes acne.

Androgenetic alopecia is also an androgen-dependent and highly genetic condition. DHT binds to ARs expressed on dermal papilla cells (DPC) in the scalp and induces AR-mediated transcription of genes that contribute to androgenic alopecia. Clascoterone blocks the interaction between DHT and ARs, and so it inhibits AR-regulated transcription and DHT-induced IL-6 synthesis.