XAT-14

XAT-14 is a Furanocoumarin derivative. XAT-14 competes with agonists to bind to the active pocket of MRGPRX2, inhibiting calcium influx and mast cell degranulation. XAT-14 suppresses the release of histamine, IL-8 and MCP-1 induced by Compound 48/80. XAT-14 inhibits local allergic inflammation. XAT-14 can be used for the research of pseudo-allergic diseases ^[1].

In Vivo, XAT-14 (4-16 mg/kg) reduces the degree of hindlimb swelling and Evans blue extravasation induced by C48/80 in mice^[1].

In Vitro, XAT-14 (100 μM) shows no cytotoxicity in LAD2 cells^[1]. XAT-14 (25-100 μM) potently inhibits Compound 48/80-induced β-hexosaminidase release in LAD2 cells, with an IC₅₀ of 22.95 μM, and exhibits superior efficacy to Imperatorin ^[1]. XAT-14 (25-100 μM) dose-dependently inhibits Compound 48/80-induced release of histamine, IL-8 and MCP-1 in LAD2 cells^[1]. XAT-14 (25-100 μM) inhibits Compound 48/80-induced calcium influx in MRGPRX2-HEK293 cells in a dose-dependent manner, indicating that its effect is mediated through the MRGPRX2 signaling pathway^[1].

References:
[1]. Yang W, et al. Furanocoumarin derivatives inhibit MRGPRX2-mediated pseudo-allergy. Bioorganic & medicinal chemistry letters. 2026 Jun;135:130589.