The antiproliferative effect of vitamin D-3 analogues

1,25-Dihydroxyvitamin D. (VD), the biologically active metabolite of vitamin D is well known to regulate calcium homoeostasis, but the hormone can also regulate cellular growth: at the beginning of the 1980s, VD was been shown to induce differentiation and to inhibit proliferation of several normal and malignant cell types [1, 2], Thus, VD would be an interesting drug against hyperproliferative diseases like psoriasis and cancer [31, if side-effects, like hy-percalcaemia. hypercalciuria and soft tissue calcification [41 caused by the hormone's classical action, were brought under control. This led to the development of VD analogues with low calcaemic effect and/or high potency on growth arrest, and in total more than 1,000 compounds have yet been synthesized by various academic and industrial institutions [5-8], The majority of them have a modification in the side chain. Two compounds, calcipotriol (MC903: Leo) and tacalcitol l.24(R)-dihydroxyvitamin D,; Teijin], are already commercially available for the topical treatment of psoriasis and the second generation of even more potent analogues are on clinical trial. © 1996 S. Karger AG, Basel.