Glucocorticoid antagonists and 11β-HSD1 inhibitors

Glucocorticoid action has been linked to the development of the metabolic syndrome. Therefore, glucocorticoid blockade is an attractive strategy to treat metabolic disorders. One interesting approach is to develop glucocorticoid receptor antagonists with properties for liver-specific delivery. These compounds reduce hyperglycemia with minimal risk of HPA axis activation. Additional strategies involve the use of a ketoconazole enantiomer to inhibit glucocorticoid biosynthesis, and 11β-hydroxysteroid dehydrogenase (11β) inhibitors to suppress the regeneration of active glucocorticoids in tissues.

Section editors:Ramakanth Sarabu and Jefferson W. Tilley – Roche Research Center, Nutley, NJ 07110, USA