Glucocorticoid receptor modulators CpdX and CpdX-D3 exhibit the same in vivo antiinflammatory activities as synthetic glucocorticoids.
Fiche publication
Date publication
juin 2019
Journal
Proceedings of the National Academy of Sciences of the United States of America
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre
Tous les auteurs :
Hua G, Zein N, Daubeuf F, Chambon P
Lien Pubmed
Résumé
We previously reported that the nonsteroidal compound CpdX, which was initially characterized 20 y ago as a possible gestagen and, shortly afterward, as a possible drug for treatments of inflammatory diseases, selectively triggers the NFκB/AP1-mediated tethered indirect transrepression function of the glucocorticoid receptor (GR), and could therefore be a selective glucocorticoid receptor agonistic modulator (SEGRAM). We now demonstrate that, upon administration to the mouse, CpdX and one of its deuterated derivatives, CpdX-D3, repress as efficiently as a synthetic glucocorticoid (e.g., Dexamethasone) an induced skin atopic dermatitis, an induced psoriasis-like inflammation, a house dust mite (HDM)-induced asthma-like allergic lung inflammation, a collagen-induced arthritis, an induced ulcerative colitis, and an ovalbumin-induced allergic conjunctivitis. Interestingly, in the cases of an HDM-induced asthma-like allergic lung inflammation and of a collagen-induced arthritis, the CpdX antiinflammatory activity was selectively exerted by one of the two CpdX enantiomers, namely, CpdX(eA) or CpdX-D3(eA).
Mots clés
CpdX, antiinflammatory drug, glucocorticoids, inflammatory diseases, selective glucocorticoid receptor agonistic modulators
Référence
Proc. Natl. Acad. Sci. U.S.A.. 2019 Jun 21;: