A method for identifying small molecule compounds capable of reducing the interaction between Interleukin-23 (IL-23) and the Interleukin-23 receptor (IL-23R).

Abstract

The invention relates to a method for determining small molecule compounds capable of reducing the interaction between Interleukin-23 (IL-23) and the Interleukin-23 receptor (IL-23R) for application in the prevention or treatment of inflammatory and autoimmune diseases associated with the IL-23 / Th17 signaling axis. The method under the invention consists of exposing IL-23 or the IL-23 receptor (IL-23R) to an effective amount of a small molecule compound of formula (I) or its stereoisomers, pharmaceutical salts, hydrates or solvates. The compound described in the invention binds to the IL-23p19 subunit at the IL-23R receptor interaction region, specifically at the Site 2 interaction site, through interactions with key amino acids such as Trp156, Lys164, Glu58, and Leu160, thereby reducing or preventing the formation of the IL-23 / IL-23R complex and inhibiting IL-23 biosignature transmission. The IL-23 inhibitory activity of the compound was confirmed by competitive IL-23 / IL-23R binding ELISA assay and cell bioassay.The method described in the invention opens up the possibility of developing small molecule IL-23 inhibitors that have the potential for low-cost oral administration and a lower immunogenic risk compared to existing biological therapies.

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