Systemic administration in mice or rats indicate that SEGRAMs can diminish acute infections, rheumatoid arthritis, asthma and colitis.

[2] For example, skin atrophy in rats was significantly less pronounced than under prednisolone in a study using the SEGRAM Mapracorat, and metabolic effects like weight gain or increase of blood glucose were practically inexistent.

[11] In the absence of glucocorticoids, the GR resides in the cytosol in an inactive state complexed with heat shock proteins (HSPs) and immunophilins.

The activated GR can then regulate gene expression via one of two pathways:[10] Hence the anti-inflammatory effects of glucocorticoids results from both transactivation and transrepression.

In contrast, studies in rats and mice have shown that most of the side effects of glucocorticoids, such as diabetogenic activity, osteoporosis, as well as skin atrophy, are mainly caused by transactivation.

One was a double blind dose finding study for an ointment against atopic dermatitis conducted by Intendis, a part of Bayer HealthCare Pharmaceuticals specialized on dermatology.

[18] A Phase III trial started in November 2010, evaluating an ophthalmic suspension for the treatment of inflammation following cataract surgery, conducted by Bausch & Lomb.

[19] A phase II trial with another dissociated glucocorticoid fosdagrocorat (PF-04171327) (a phosphate ester prodrug of dagrocorat (PF-00251802)[20][21]) for rheumatoid arthritis was started in 2011 by Pfizer.

In chronic inflammatory diseases like atopic dermatitis (skin), rheumatoid arthritis (joints),..., the side effects of corticosteroids are problematic because of the necessary long-term treatment.

Systemic long-term treatment of inflammations with corticosteroids is particularly liable to cause metabolic side-effects, which makes the development of oral SEGRAMs an interesting goal.

[23] It remains to be seen whether selective receptor agonists or modulators indeed cause significantly less side-effects than classical corticoids in clinical applications.