Characterization of a novel non-steroidal glucocorticoid receptor agonist optimized for topical treatment

Glucocorticoids (GCs) are commonly used topical treatments for skin diseases but are associated with both local and systemic side effects. In this study, we describe a selective non-steroidal glucocorticoid receptor (GR) agonist for topical use, LEO 134310, which is rapidly deactivated in the blood resulting in low systemic exposure and a higher therapeutic index in the TPA-induced skin inflammation mouse model compared with betamethasone valerate (BMV) and clobetasol propionate (CP). Selectivity of LEO 134310 for GR was confirmed within a panel of nuclear receptors, including the mineralocorticoid receptor (MR), which has been associated with induction of skin atrophy. Topical treatment with LEO 134310 in minipigs did not result in any significant reduction in epidermal thickness in contrast to significant epidermal thinning induced by treatment with BMV and CP. Thus, the profile of LEO 134310 may potentially provide an effective and safer treatment option for skin diseases compared with currently used glucocorticoids.

Automated summary

This study describes a selective non-steroidal glucocorticoid receptor (GR) agonist, LEO 134310, for topical use, which is rapidly deactivated in the blood resulting in low systemic exposure and a higher therapeutic index compared with currently used glucocorticoids. The selectivity of LEO 134310 for GR was confirmed within a panel of nuclear receptors, and topical treatment with LEO 134310 in minipigs did not result in significant epidermal thinning.