These potent anti-inflammatory compounds have been designed to treat inflammatory conditions but with reduced, serious side effects associated with the long-term use of traditional glucocorticoid drugs. Glucocorticoids are one of the most prescribed drug classes due to their remarkable anti-inflammatory properties and are used to treat acute and chronic inflammatory diseases, such as asthma, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and atopic dermatitis. But, despite their efficacy and broad therapeutic spectrum, undesired negative side effects restrict long-term systemic and local treatments with the currently available glucocorticoid drugs.
Chronic treatment with glucocorticoids can induce insulin resistance, leading to reduced glucose uptake in the primary organ for glucose disposal, the skeletal muscle, facilitating muscle wasting. These side effects are due to decreased protein synthesis and increased protein degradation, leading to cachexia and, muscle atrophy. They also cause growth retardation in children, osteoporosis, and skin effects, including skin thinning and impaired wound healing. An incomplete understanding of the molecular mechanisms through which glucocorticoids mediate activity via the glucocorticoid receptor has impaired efforts to develop improved glucocorticoids. There is a need for dissociated glucocorticoid compounds with improved therapeutic activity and reduced undesirable side effects.
Researchers at the University of Florida have identified two rationally developed anti-inflammatory compounds, SR16024 and SR11466. Both novel molecules act through the glucocorticoid receptor, but in animal models show reduced side effects associated with long-term use of glucocorticoids. The compounds possess dissociated activity, enabling the treatment of inflammatory diseases without negatively impacting muscle mass and with improved effects on osteoblast mineralization and glucose disposal. These novel anti-inflammatory agents can potentially replace existing drugs such as cortisone, hydrocortisone, and prednisone.
New glucocorticoid compounds for treating inflammatory conditions, but with reduced, negative side effects, including Duchenne muscular dystrophy
These two new glucocorticoids, SR16024 and SR11466, potentially enable the treatment of inflammatory and autoimmune conditions without leading to undesired side effects, such as muscle wasting and cachexia. Glucocorticoids exert their effects by binding and activating the glucocorticoid receptor. Additionally, the compounds present the potential for treating and ameliorating symptoms of Duchenne muscular dystrophy, for which glucocorticoids are the only treatment, but lead to growth retardation and bone fractures.