The physiologically active form of vitamin D, 1,25-dihydroxyvitamin D 3 , plays an important role not only in the establishment and maintenance of calcium metabolism, but also in regulating cell growth and differentiation. Because the clinical usefulness of 1,25-dihydroxyvitamin D 3 is limited by its tendency to cause hypercalcemia, new analogs with a better therapeutic profile have been synthesized, including ZK 156718. We compared the effects of 1,25-dihydroxyvitamin D 3 and ZK 156718 on growth, differentiation, and on p21 W a f 1 / C i p 1 and p27 K i p 1 expression in human colon cancer cells (Caco-2). Whereas ZK 156718 at the concentration [10 - 8 M] was as potent as 10 - 6 M 1,25-dihydroxyvitamin D 3 in inducing differentiation and p21 W a f 1 / C i p 1 expression, it was even more effective in inhibiting cell growth and stimulating p27 K i p 1 expression than 1,25-dihydroxyvitamin D 3 itself. In summary, our study presents a new and potent vitamin D analog with a decreased metabolic stability, making it useful for the treatment of a diversity of clinical disorders.