Light-Regulated Agonists Spatiotemporally Activating the Vitamin D Receptor Mitigate Psoriasis-like Inflammation in Mice without Inducing Hypercalcemia.

ABSTRACT: Vitamin D receptor (VDR) activation has demonstrated beneficial effects on psoriasis. However, its crucial role in calcium metabolism limits clinical applications due to the risk of health-threatening dysregulation in serum calcium. In the present study, we have designed, synthesized, and biologically tested highly potent light-controllable VDR agonists containing a photoswitchable azobenzene moiety in the drug scaffold. The optimized molecule PhotoVDRM is inactive in the dark and can be selectively activated with light using specific wavelengths, including nonphototoxic visible blue light and UVB that is currently used in skin treatments. We used a modified hydrogen/deuterium exchange method to identify the binding site and study VDR dynamics upon ligand binding. Importantly, testi

SUBMITTER: Rovira X 

PROVIDER: S-EPMC12746157 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature