Therapeutic applications for novel non-hypercalcemic vitamin D receptor ligands

Mihwa Choi, Makoto Makishima

Research output: Contribution to journalReview articlepeer-review

37 Scopus citations


Background: The active form of vitamin D3, 1α,25- dihydroxyvitamin D3 (1,25(OH)2D3), plays an important role in calcium homeostasis, cell differentiation, cell proliferation and immunity. A more complete understanding of the several physiological and pharmacological properties of 1,25(OH)2D3 indicates that the vitamin D receptor (VDR) is a promising drug target in the treatment of cancers, autoimmune diseases, infections and cardiovascular disease as well as bone and mineral disorders. The calcemic effect of 1,25(OH)2D 3 and its derivatives has limited their clinical application. As a result, the development of non-calcemic VDR ligands is required to realize the potential of VDR-targeting therapy. Objective: In this review, we discuss the in vitro and in vivo pharmacological actions, including VDR interaction, regulation of cofactor recruitment, pharmacokinetics and cell type or tissue-selective action of VDR ligands with less-calcemic activity. Conclusion: Pharmacokinetic parameters and selective tissue accumulation are related to the therapeutic benefit of non-hypercalcemic vitamin D derivatives. Induction of distinct VDR conformations and cofactor recruitment may be associated with selective actions of non-secosteroidal VDR ligands. Derivatives of lithocholic acid, a newly identified endogenous VDR ligand, are less-calcemic VDR ligands.

Original languageEnglish (US)
Pages (from-to)593-606
Number of pages14
JournalExpert Opinion on Therapeutic Patents
Issue number5
StatePublished - May 2009
Externally publishedYes


  • Autoimmune disease
  • Bile acid
  • Cancer
  • Hypercalcemia
  • Infection
  • Osteoporosis
  • Parathyroid hormone
  • Vitamin D
  • Vitamin D receptor

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery


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