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Dissociated non-steroidal glucocorticoids: tuning out untoward effects

The endogenous glucocorticoid (GC), cortisol, is involved in maintaining homeostatic balance in glucose regulation and immune response while allowing stress adaptation. The glucocorticoid receptor (GR) is required to maintain life and is the target of numerous FDA-approved drugs. Synthetic steroidal GCs are useful in a plethora of conditions characterized by excessive inflammatory or immune responses. Unfortunately, the GCs used at present have potentially dose-limiting and debilitating side effects, some of which derive from the glucose regulatory role of GCs. Consequently, there is a great need to find agents which preserve the potent immune effects without the side effects. This manuscript reviews the existing patent literature on these intensely sought non-steroidal agents that dissociate the therapeutic from metabolic effects, or specifically retain certain GR target effects with attenuated untoward effects. The chemical classes and underlying mechanisms (when known) for these non-steroidal GCs are discussed.