Demonstrates light-controlled effects on vitamin D receptor activity in cells, indicating new therapeutic possibilities.
The secosteroid vitamin D (vitD) is essential for human health, maintaining bone metabolism, calcium homeostasis, and immune function via the vitamin D receptor (VDR). VDR activation has complex and cell-specific effects in multiple tissues and spatial control of VDR activity is desirable. Here, we developed vitD mimetics bearing a photo-switchable azobenzene motif to achieve spatiotemporal resolution in VDR activation. Structure-guided tuning of regiochemistry and H-bonding motifs provided a potent and selective vitD mimetic that can be reversibly switched in cellulo between agonist and antagonist states with light. In a model of osteogenesis, this unique bidirectional precision tool mediated light-dependent osteogenic and osteolytic effects.
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Ge et al. (2026) studied this question.
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