New glucocorticoids on the horizon: repress, don't activate!

Glucocorticoids are highly effective drugs; their immunosuppressive and antiinflammatory actions are used in the treatment of many rheumatic and other inflammatory diseases. However, their use is sometimes considerably limited by numerous adverse reactions. For this reason, great efforts have been made in recent years to develop innovative glucocorticoids or glucocorticoid receptor ligands that have improved therapeutic effect/adverse reaction ratio. We summarize the position and critically discuss the following products that are currently under development: (1) selective glucocorticoid receptor agonists (SEGRA or dissociating glucocorticoids); (2) nitrosteroids; and (3) long-circulating liposomal glucocorticoids. Finally, we describe the state of research on membrane-bound glucocorticoid receptors as possible further targets for specific glucocorticoid actions.