EB-1089, A NOVEL VITAMIN-D ANALOG WITH STRONG ANTIPROLIFERATIVE AND DIFFERENTIATION-INDUCING EFFECTS ON TARGET-CELLS

The physiologically active form of vitamin D, 1 alpha,25-dihydroxyvita min D-3, plays an important role not only in the establishment and mai ntenance of calcium metabolism, but also in regulating cell growth and differentiation. As the clinical usefulness of 1 alpha,25-dihydroxyvi tamin D-3 is limited by its tendency to cause hypercalcemia, new analo gs with a better therapeutic profile have been synthesized. One of the se new synthetic vitamin D analogs is EB 1089, which is characterized by an altered side chain structure featuring 26,27-dimethyl groups and two double bonds. This analog has been shown to be more potent than 1 ,25-dihydroxyvitamin D-3 in inhibiting proliferation, stimulating diff erentiation, and inducing apoptosis in a number of different cell type s, including cancer cells. Despite being more potent than 1 alpha,25-d ihydroxyvitamin D-3 with respect to its cell regulatory effects, EB 10 89 displays weaker calcemic side-effects. These characteristics make E B 1089 a potentially useful compound for the treatment of a diversity of clinical disorders, including cancer and metabolic bone diseases. A promising phase I study with EB 1089 in patients with advanced breast and colon cancer has already been carried out, and more clinical tria ls evaluating the clinical effectiveness of EB 1089 in other types of cancer are in progress. (C) 1997 Elsevier Science Inc.