Vitamin D Analogs and Coactivators

Abstract

The secosteroid hormone 1α,25-dihydroxyvitamin D₃ [1,25-(OH)₂D₃] has potent antiproliferative and prodifferentiating actions on a wide variety of normal as well as malignant cell types. Strong calcemic effects obstruct the actual application of 1,25-(OH)₂D₃ for the treatment of hyperproliferative disorders such as cancer. To overcome this problem, structural analogs of 1,25-(OH)₂D₃ have been designed with a clear dissociation between antiproliferative and calcemic effects. This review focuses on the molecular mode of action of different 1,25-(OH)₂D₃ analogs and, in particular, on the recruitment of cofactor molecules to the vitamin D receptor by these analogs.