IL-23 receptor

Class

IL-23R antagonist (oral peptide)

Pathway

IL-23 / Th17

Notes

Blocks the receptor directly, unlike the p19-targeting mAbs (risankizumab/guselkumab/mirikizumab) already in the pathway. | original target text: IL-23 receptor (IL-23R)

The interleukin-23 receptor (IL-23R) is part of a two-chain receptor complex expressed on a subset of immune cells, especially T-helper 17 (Th17) cells and related innate lymphoid cells. When the cytokine IL-23 binds this receptor, it triggers an intracellular signaling cascade that drives these cells to survive, expand, and release inflammatory mediators such as interleukin-17 and interleukin-22. This IL-23/Th17 axis is a central driver of chronic inflammatory diseases including psoriasis, psoriatic arthritis, and inflammatory bowel disease. Most existing therapies in this pathway are injectable monoclonal antibodies that bind the p19 subunit of the IL-23 cytokine itself, preventing it from being formed or from reaching its receptor. An alternative strategy is to block the receptor directly, using a small molecule or peptide that occupies the binding site on IL-23R so the cytokine cannot engage it, regardless of how much cytokine is present. Designing such an antagonist as an oral peptide is notable because peptides are typically administered by injection; an orally delivered version could offer a non-injectable option and, depending on its absorption profile, may act preferentially within the gastrointestinal tract, which is relevant for intestinal inflammatory conditions.