Therapeutic application of vitamin D receptor ligands: an updated patent review

The vitamin D receptor (VDR) is a promising drug target in the treatment of cancer, autoimmune disease, inflammation, infection and cardiovascular disease, as well as bone and mineral disorders. Although many VDR ligands have been developed and shown to activate VDR in vitro and in vivo, including vitamin D derivatives and non-secosteroidal compounds, a principal adverse effect of hypercalcemia has limited their clinical application.

We summarize recent patent activity regarding VDR ligands, including vitamin D derivatives, non-secosteroidal compounds and tissue-selective prodrugs, alongside their therapeutic applications. The potential for use of VDR ligands in the treatment of hepatic fibrosis, pancreatic fibrosis and neuronal disease is also reviewed.

Several VDR ligands have been shown to have increased therapeutic efficiency in experimental models of cancer, inflammation and cardiovascular disease, and to exhibit function-selective and/or tissue-selective activity. The underlying molecular and pharmacological mechanisms remain to be elucidated. Further studies, both basic and applied, should make successful VDR-targeting therapy possible.