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Updated: Feb 12, 2026

Quantifying Agonist Activity at G Protein-coupled Receptors
Published on: December 26, 2011
Sulfoximines as potent RORγ inverse agonists
Gilles Ouvry1, Franck Bihl1, Claire Bouix-Peter1
1Nestlé Skin Health, Les Templiers 2400 Route des Colles, 06410 Biot, France.
Abstract:
Progress in the identification of suitable RORγ inverse agonists as clinical candidates has been hampered by the high lipophilicity that seems required for high potency on this nuclear receptor. In this context, we decided to focus on the replacement of the hydroxymethyl group found on known modulators to determine if more polarity could be tolerated in this position. SAR of the replacement of this moiety is presented in this article leading to the identification of sulfoximine derivatives as potent modulators with pharmacological activity in the in vivo mouse Imiquimod psoriasis model.
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