ZK 156718, a low calcemic, antiproliferative, and prodifferentiating vitamin D analog

Biochem Biophys Res Commun. 2002 Jan 11;290(1):504-9. doi: 10.1006/bbrc.2001.6213.


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(Waf1/Cip1) and p27(Kip1) 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(Waf1/Cip1) expression, it was even more effective in inhibiting cell growth and stimulating p27(Kip1) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caco-2 Cells
  • Calcitriol / pharmacology
  • Calcium / metabolism
  • Calcium Channel Agonists / pharmacology
  • Cell Cycle Proteins / biosynthesis
  • Cell Differentiation
  • Cell Division
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclins / biosynthesis
  • Detergents / pharmacology
  • Dose-Response Relationship, Drug
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Immunoblotting
  • Models, Chemical
  • Octoxynol / pharmacology
  • Protein Binding
  • Time Factors
  • Tumor Suppressor Proteins / biosynthesis
  • Vitamin D / analogs & derivatives*
  • Vitamin D / chemistry
  • Vitamin D / pharmacology*


  • CDKN1A protein, human
  • Calcium Channel Agonists
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Detergents
  • Tumor Suppressor Proteins
  • ZK 156718
  • Vitamin D
  • Cyclin-Dependent Kinase Inhibitor p27
  • Octoxynol
  • Calcitriol
  • Calcium