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Review

Non-steroidal glucocorticoid receptor antagonists: the race to replace RU-486 for anti-glucocorticoid therapy

, , , &
Pages 59-81 | Published online: 03 Jan 2007
 

Abstract

The endogenous glucocorticoid, cortisol, elevates blood glucose and suppresses the immune system. Glucocorticoid (GC) levels rapidly increase in response to physiologic and mental stress, thereby allowing stress adaptation. Unfortunately, the GC response can be excessive, especially under stressful conditions for the organism. The resulting hypercortisolemia is associated with a cluster of symptoms called Cushing’s syndrome, a serious and potentially fatal illness involving hyperglycemia, hypertension, osteoporosis, muscle atrophy and fat maldistribution, as well as psychoses and immunosuppresion. Several disease states, such as diabetes and Cushing’s, would benefit from blocking the actions of endogenous cortisol. The only glucocorticoid receptor (GR) antagonist available in the clinic is the steroid mifepristone (RU-486), whose primary potency is antigestagenic, making its utility as a GR antagonist limited. This manuscript reviews the current patent literature on selective non-steroidal GR antagonists.

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