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Updated: Sep 27, 2026

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Rational design of vitamin D3 analogues which selectively restore activity to a vitamin D receptor mutant associated
Steve L Swann1, Joel J Bergh, M Cindy Farach-Carson
1Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, USA.
Abstract:
[formula: see text] Vitamin D3-resistant rickets (VDRR) is associated with mutations to the Vitamin D receptor (VDR) which effect ligand-dependent transactivation. Some VDRR associated mutants directly disrupt ligand binding. Using the reported VDR-1,25-dihydroxy vitamin D3 (1,25(OH)2D3) cocrystal structure, three 1,25(OH)2D3 analogues were designed to uniquely complement the rickets associated mutant VDR(Arg274-->Leu). The three analogues were 17 to 286 times more potent than 1,25(OH)2D3 with the mutant in cell-based assays and did not substantially activate cellular calcium influx.
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