[Recent progress of study on vitamin D analogs]

Separation of inducing cell differentiation and antiproliferative activities as well as immunoregulatory effects from calcemic activity of the natural hormone, 1alpha,25-dihydroxyvitamin D(3) [1alpha,25 (OH) (2)D(3)] , utilizing the synthetic 1alpha,25 (OH) (2)D(3) analogs has been studied over 20 years. During the past two decades, progress of molecular biology taught us the precise action mechanisms of 1alpha,25 (OH) (2)D(3) through its specific receptor to express the target genes on the molecular level. Modification at the CD-ring side chain of 1alpha,25 (OH) (2)D(3) is the most common chemical conversion, and the alternative approach is A-ring and/or CD-ring modifications. With these chemical functionalizations, some vitamin D analogs are clinically used as medicines or promising candidates for treating secondary hyperparathyroidism, psoriasis, and osteoporosis. Although 1alpha,25 (OH) (2)D(3) can inhibit the growth of various human cancers and regulate the human immune system, primary side effect of 1alpha,25 (OH) (2)D(3) is its tendency to raise serum calcium levels and to cause hypercalcemia, which should be avoided. With these backgrounds, we discuss here recent progress on synthetic vitamin D analogs.