An orally active, gut-enriched AhR agonist demonstrates therapeutic efficacy in colitis through regulation of inflammation, barrier homeostasis, and fibrosis

Current therapies primarily target inflammatory pathways and rarely achieve durable remission or structural disease modification, highlighting a major unmet clinical need. Here, we evaluated the therapeutic potential of YUQ-A1007, an orally active, gut-enriched small-molecule aryl hydrocarbon receptor (AhR) agonist, across multiple translational models of colitis.

The anti-inflammatory, barrier-restorative, and anti-fibrotic effects of YUQ-A1007 were assessed using in vitro cell systems, patient-derived colonic biopsies and organoids, permeability assays, and three murine colitis models. YUQ-A1007 partially activated AhR signalling, suppressed pro-inflammatory cytokine production, enhanced regulatory T cell differentiation, increased tight junction protein expression, and inhibited fibrotic gene programs.