Desisobutyryl-ciclesonide

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)