Z-3578 is a small-molecule antagonist targeting MrgX2 (Mas-related G protein-coupled receptor X2) with significant anti-pseudoallergic activity and a KD value of 729 nM. Z-3578 effectively inhibits mast cell degranulation induced by substance P (SP) and C48/80, suppressing the release of beta-hexosaminidase with IC50 values of 4.90 µM and 6.18 µM, respectively. It also markedly reduces the release of histamine and TNF-alpha, along with intracellular calcium flux. In a murine pseudoallergy model, Z-3578 significantly alleviates paw swelling and dye extravasation and lowers serum histamine levels, indicating potent in vivo anti-allergic effects. Z-3578 holds promise as a lead compound for the treatment of allergic diseases, especially pseudoallergic reactions[1].
