Rational Design of a Topical Androgen Receptor Antagonist for the Suppression of Sebum Production with Properties Suitable for Follicular Delivery

In 2010, researchers developed a novel nonsteroidal androgen receptor antagonist, compound 1, for topical control of sebum production. The compound was designed to be delivered preferentially by the follicular route to the pilosebaceous unit, the site of action. It was found to be potent, selective, and efficacious in the golden Syrian hamster ear animal model, binding to the human androgen receptor with an IC50 = 100 nM and showing 44-fold selectivity versus the progesterone receptor. The compound was designed to be rapidly cleared with low systemic exposure. In the hamster ear model, it was a potent inhibitor of wax ester production with an ED50 = 0.2% (0.02 mg/cm², BID application for 2 weeks). The reduction in sebaceous gland size and wax ester production were fully reversible after 2 weeks of application.