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Curr Opin Investig Drugs. 2005 May;6(5):503-7.

Dissociated glucocorticoid receptor ligands: compounds with an improved therapeutic index.

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  • 1Schering AG, RBA Dermatology Europe, 13342 Berlin, Germany.


Glucocorticoids are well known for their potent anti-inflammatory and immunosuppressive actions. However, due to their potential to induce serious undesired effects, there is a great need for compounds with a better therapeutic index. Recent discoveries have demonstrated that the positive and negative regulation of gene expression via the glucocorticoid receptor is mediated by different mechanisms. This regulation is predominantly responsible for either anti-inflammatory effects or certain side effects, depending on whether it is negative or positive. Compounds that preferentially induce transrepression rather than transactivation should be superior to classical glucocorticoids. Indeed, proof of concept has been recently achieved with such selective glucocorticoid receptor agonists.

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