Mechanisms for the selective action of Vitamin D analogs

• Published in: Journal of steroid biochemistry and molecular biology Vol. 97; no. 1; pp. 21 - 30
• Main Authors: Bouillon, Roger, Verlinden, Lieve, Eelen, Guy, De Clercq, Pierre, Vandewalle, Maurits, Mathieu, Chantal, Verstuyf, Annemieke
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Oxford Elsevier Ltd 01.10.2005; Elsevier Science
• Subjects: Analogs; Animals; Biological and medical sciences; Endocrine System - drug effects; Endocrine System - physiology; Fundamental and applied biological sciences. Psychology; Humans; Receptors, Calcitriol - metabolism; Substrate Specificity; Tissue-selective activity; Vertebrates: endocrinology; Vitamin D; Vitamin D - analogs & derivatives; Vitamin D - chemistry; Vitamin D - pharmacology; Vitamin D - therapeutic use; Analogs; Vitamin D; Tissue-selective activity; Analog
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2005.06.013

The non-classical effects of 1,25(OH) 2D 3 create possible therapeutic applications for immune modulation (e.g. auto-immune diseases and graft rejection), inhibition of cell proliferation (e.g. psoriasis, cancer) and induction of cell differentiation (e.g. cancer). The major drawback related to the use of 1,25(OH) 2D 3 is its calcemic effect, which prevents the application of pharmacological concentrations. Several analogs are now available that show modest to good selectivity with regard to specific effects (e.g. anticancer or immune effects or bone anabolism versus hypercalcemia) when tested in appropriate in vivo models. The molecular basis for this selectivity is only partially understood and probably a variable mixture of mechanisms.