Desisobutyryl ciclesonide is a glucocorticoid receptor agonist and the active metabolite of the prodrug ciclesonide .1,2 It is formed from inhaled ciclesonide by intracellular esterases in the lung. Desisobutyryl ciclesonide binds to the glucocorticoid receptor (IC50 = 1.75 nM for the human receptor) and induces glucocorticoid receptor-mediated gene transactivation in a reporter assay. It inhibits concanavalin A-induced proliferation of primary rat spleen cells and human peripheral blood mononuclear cells (PBMCs; IC50s = 1.5 and 1.3 nM, respectively). Desisobutyryl ciclesonide also inhibits CD3-induced proliferation of human CD4+ lymphocytes (IC50 = 0.2 nM) and the production of cytokines in the same cells (IC50s = 0.5-1.5 nM).3 It reduces eosinophil, TNF-α, and total protein accumulation in bronchoalveolar lavage fluid (BALF) of rats sensitized and challenged with ovalbumin (ED50s = 0.7, 0.4, and 0.5 mg/kg, respectively).
1.Belvisi, M.G., Bundschuh, D.S., Stoeck, M., et al.Preclinical profile of ciclesonide, a novel corticosteroid for the treatment of asthmaJ. Pharmacol. Exp. Ther.314(2)568-574(2005) 2.Joshi, T., Johnson, M., Newton, R., et al.An analysis of glucocorticoid receptor-mediated gene expression in BEAS-2B human airway epithelial cells identifies distinct, ligand-directed, transcription profiles with implications for asthma therapeuticsBr. J. Pharmacol.172(5)1360-1378(2015) 3.Stoeck, M., Riedel, R.T., Hochhaus, G., et al.In vitro and in vivo anti-inflammatory activity of the new glucocorticoid ciclesonideJ. Pharmacol. Exp. Ther.309(1)249-258(2004)