Discovery of an Androgen Receptor Degrader Featuring a Pyridazinyl Glutarimide CRBN-Binding Motif for Transdermal Treatment of Androgenetic Alopecia

The study presents the discovery of a novel androgen receptor degrader, featuring a pyridazinyl glutarimide CRBN-binding motif, for the transdermal treatment of androgenetic alopecia. The compound, referred to as dAR-6-1, was evaluated through various tests, including HTRF CRBN affinity testing, aqueous solubility testing, and pharmacokinetic comparisons with clinically approved transdermal drugs. Preliminary results showed effective androgen receptor degradation and modulation of downstream signaling in hDPC cells. Additionally, a local safety evaluation was conducted after 28-day repeated topical administration, indicating promising potential for treating androgenetic alopecia. The study also validated the AGA mouse model via AR expression in the skin, supporting the compound's efficacy and safety for further development.