Expert opinion on investigational drugs vol:9 issue:3 pages:443-55
The non-classical effects of 1alpha,25-dihydroxyvitamin D(3) (1alpha, 25(OH)(2)D(3)) create possible therapeutic applications for immune modulation (e.g., autoimmune 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 1alpha,25(OH)(2)D(3) is its calcaemic effect, which prevents the application of pharmacological concentrations. Intensive research has led to the development of analogues of 1(2)D(3) characterised by a clear dissociation of the antiproliferative and prodifferentiating capacity from the calcaemic effects. Due to this dissociation, these analogues can be used not only for the treatment of bone disorders but also for non-classical applications. In the present review, a summary is given on the use of the 1alpha,25(OH)(2)D(3) analogues for the treatment of cancer, skin and immune disorders and for the prevention of graft rejection. Moreover a brief overview is given on the use of analogues for secondary hyperparathyroidism.