The atypical retinoid E-3-(3'-Adamantan-1-yl-4'-methoxybiphenyl-4-yl)-2-propenoic acid (ST1898) displays comedolytic activity in the rhino mouse model.

ABSTRACT

Retinoids represent the first-line therapy for the treatment of acne vulgaris. Their effect is comedolytic and anti-comedogenic, and associates with hyperplasia and deregulated differentiation of the epidermis, and decreased inflammation. We here tested the comedolytic effect of the novel atypical retinoid E-3-(3'-Adamantan-1-yl-4'-methoxybiphenyl-4-yl)-2-propenoic acid (ST1898) in the rhino mouse, as a model of comedogenic acne, and compared this effect to that of adapalene (Differin® gel), as reference compound. Topical administration of 0.1% ST1898 for three weeks exerted a comedolytic effect comparable to that of adapalene 0.1%. In ST1898-treated mice, epidermal hyperplasia was significantly reduced and the expression of keratinocyte differentiation markers was less perturbed compared to adapalene-treated animals. Moreover, keratin 6, which stains activated keratinocytes, was strongly and uniformly induced in interfollicular epidermis of adapalene-treated mice, while only faintly and focally expressed in ST1898-treated ones. Our data indicate that ST1898 has strong comedolytic activity but modest topical side effects.