Abstract
Background: Glucocorticoids exert a wide range of physiological effects. They effectively control various inflammatory and autoimmune diseases and play an important role in organ transplantation. Glucocorticoids are associated with unfavorable side effects that restrict their utilization. The most undesirable side effects are related to the transactivation of target genes. On the other hand, the transrepression of the genes is also responsible for the anti-inflammatory and immunomodulator of glucocorticoids.
 Principal Findings: The separation between these two processes through alteration in glucocorticoid receptor resulting in a compound with similar GCs benefit activity with fewer side effects. This review will discuss the molecular mechanism and summarizes the most common compounds and their beneficial effect in preclinical experiments.
 Conclusion: Several compounds that possess this feature are tested in preclinical experiments with promising results. These compounds are expected to be a better alternative to GCs drugs in the management of different diseases with a high degree of effectiveness.
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