Glucocorticoids belong to a class of corticosteroids, a kind of steroid hormones. They function by binding to the glucocorticoid receptor (GR). So, these steroid hormones play important role in the immune system. They are partial feedback mechanism to cause reduced aspects of immune function.
Once glucocorticoid binds to glucocorticoid receptor, activation of the receptor happens. Then the complex enhances the expression of anti-inflammatory proteins and inhibits that of proinflammatory proteins. Thus, glucocorticoid receptor agonist has the potential in the treatment of inflammatory disease.
GW-870086 is a potent anti-inflammatory agent, and a partial agonist of glucocorticoid receptor. It is a derivate of fluticasone. The agonist binds to GR in the cell, exhibits a pIC50 of 8.2 in the displacing glucocorticoid from GR.
In A549 cells, GW-870086 possesses active effect on NF-κB with a pIC50 of 10.1. IL-6 is a pro-inflammatory cytokine and NF-κB regulates its expression. GW-870086 inhibits the production of IL-6 in a dose-dependent manner. Furthermore, GW-870086 exhibits transrepressive activity, down-regulates steroid- responsive genes in A549 cells.
What’s more, GW-870086 suppresses TNF-α-induced IL-8 secretion. It shows selective pharmacology in mouse. GW-870086 induces MMTV activity with a pEC50 of 9.6.
In addition, GW-870086 exhibits excellent anti-inflammatory effect on animals. It is administrated topically onto the skin or into the lungs of mice. As a result, the agonist dose-dependently inhibits inflammation.
In summary, GW-870086 is a potent anti-inflammatory agent, acts as a glucocorticoid receptor agonist.
References:
1. Uings IJ, et al. Br J Pharmacol. 2013 Jul;169(6):1389-403.