Recent Progress in the Discovery of Novel Glucocorticoid Receptor Modulators

Hidenori      Takahashi; Hossein      Razavi; David      Thomson

doi:10.2174/156802608783955737

Abstract

Glucocorticoids have been used in modern clinical practice for over fifty years. Although they have demonstrated potent anti-inflammatory and immunosuppressive activities, their association with debilitating and lifethreatening side effects has been a major drawback. Recent insights into glucocorticoid biology have lent support to the hypothesis that the glucocorticoid anti-inflammatory activities could be dissociated from their adverse side effects. Inspired by these biological findings, the search for dissociated glucocorticoid receptor agonists has intensified. Antagonists of the glucocorticoid receptor that offer therapeutic benefits for the treatment of diseases such as diabetes have also been pursued. These efforts have been partly focused on the development of tissue, especially liver, selective glucocorticoid receptor antagonists, which are thought to have improved safety profiles. This review offers a summary of the research and development activities in this field and covers journal and patent publications from 2003 to March 2006.

Keywords: Glucocorticoid, glucocorticoid receptor, transactivation, transrepression, agonist, dissociation, antagonist, tissue selectivity