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

May 2010 in “ Journal of Medicinal Chemistry ”

Lorna Helen Mitchell, Theodore M. Johnson, Guangming Lu, Daniel K. Du, Kaushik Datta, Felicity Grzemski, Veerabahu Shanmugasundaram, Julie Spence, Kim J. Wade, Zhi Wang, Kevin Jialin Sun, Kristin Lin, Lain-Yen Hu, Karen Elaine Sexton, N. Raheja, Catherine R. Kostlan, David Pocalyko

androgen receptor antagonist sebum production follicular delivery pilosebaceous unit nonsteroidal IC50 progesterone receptor wax ester production sebaceous gland androgen blocker oil production hair follicle delivery hair follicle unit inhibitory concentration oil gland

TLDR A new compound was created in 2010 that can control oil production when applied to the skin, and its effects are completely reversible after two weeks.

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.

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

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

11 citations, May 2010 in “Journal of Medicinal Chemistry”

A new compound was created in 2010 that can control oil production when applied to the skin, and its effects are completely reversible after two weeks.