Talarozole R enantiomer is a potent and selective inhibitor of cytochrome P450 26-mediated breakdown of endogenous all-trans retinoic acid.

Talarozole R enantiomer treatment increased the mRNA expression of CRABP2, KRT4, CYP26A1, and CYP26B1 dose-dependently, and decreased the expression of KRT2 and IL-1alpha compared with vehicle-treated skin. No mRNA change in retinol-metabolizing enzymes was obtained. There was no induction of epidermal thickness or overt skin inflammation in talarozole-treated skin. Immunofluorescence analysis confirmed the upregulation of KRT4 protein, but no upregulation of CYP26A1 and CYP26B1 expression was detected [1] [2].

Talarozole R enantiomer slightly diffused into the skin only when dissolved in propylene glycol, isopropyl myristate, or ethanol. Although only 0.1% of the dose applied was found in the skin itself after 12-24 h, this was sufficient to achieve local concentrations well above the half-maximal inhibitory concentration value for talarozole. The distribution of talarozole within the skin was investigated: 80% was located in the epidermis, while the remaining 20% was found in the dermis [3].