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Discovery and Characterization of CD12681, a Potent RORγ Inverse Agonist,Preclinical Candidate for the Topical Treatment of Psoriasis |
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| Authors: | Dr Gilles Ouvry Dr Nicolas Atrux‐Tallau Dr Franck Bihl Aline Bondu Dr Claire Bouix‐Peter Isabelle Carlavan Olivier Christin Marie‐Josée Cuadrado Dr Claire Defoin‐Platel Dr Sophie Deret Denis Duvert Christophe Feret Mathieu Forissier Dr Jean‐François Fournier David Froude Dr Fériel Hacini‐Rachinel Dr Craig Steven Harris Dr Catherine Hervouet Dr Hélène Huguet Guillaume Lafitte Dr Anne‐Pascale Luzy Dr Branislav Musicki Danielle Orfila Benjamin Ozello Coralie Pascau Jonathan Pascau Véronique Parnet Guillaume Peluchon Romain Pierre Dr David Piwnica Dr Catherine Raffin Patricia Rossio Delphine Spiesse Dr Nathalie Taquet Dr Etienne Thoreau Rodolphe Vatinel Dr Emmanuel Vial Dr Laurent François Hennequin |
| Affiliation: | Nestlé Skin Health R&D, Sophia-Antipolis Cedex, France |
| Abstract: | With possible implications in multiple autoimmune diseases, the retinoic acid receptor‐related orphan receptor RORγ has become a sought‐after target in the pharmaceutical industry. Herein are described the efforts to identify a potent RORγ inverse agonist compatible with topical application for the treatment of skin diseases. These efforts culminated in the discovery of N‐(2,4‐dimethylphenyl)‐N‐isobutyl‐2‐oxo‐1‐(tetrahydro‐2H‐pyran‐4‐yl)methyl]‐2,3‐dihydro‐1H‐benzod]imidazole‐5‐sulfonamide (CD12681), a potent inverse agonist with in vivo activity in an IL‐23‐induced mouse skin inflammation model. |
| Keywords: | interleukin 17 lipophilic ligand efficiency psoriasis RORγ topical application |