FXR AND PPAR LIGANDS REVEAL POTENTIAL PHARMACOLOGICAL CROSSTALK WITH MRGPRX4 IN HEPATOBILIARY PRURITUS (AASLD 2026) - Oct 6, 2026 - Abstract #49; " FXR agonists activated hMRGPRX4 in β-arrestin recruitment assays, including obeticholic acid (EC50: 23.1 μM), cilofexor (EC50: 52.1 μM) and tropifexor (EC50: 19.4 μM). Conversely, selected PPAR agonists inhibited agonistinduced hMRGPRX4 activation, including seladelpar (IC50: 2.25 μM), fenofibrate (IC50: 2.89 μM), elafibranor (IC50: 3.26 μM) and, with lower potency, bezafibrate (IC50: 83.2 μM)... This study identified clinically relevant nuclear receptor ligands as modulators of MRGPRX4. FXR agonist engagement of MRGPRX4 may contribute to hepatobiliary itch, while PPAR agonist-mediated MRGPRX4 inhibition could explain antipruritic effects and suggest repurposing opportunities for other itchentities. Functional interplay between MRGPRX4, FXR and PPAR pathways in hepatobiliary pruritus warrants further investigation."
Dermatology • Hepatology • Pruritus
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Silvia Pickering1; Giulia Pontarollo1; Dominik Thimm2; Christa Müller2; Andreas Kremer3
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