c48/80

Compound 48/80 trihydrochloride (C48/80 trihydrochloride) is a mixture of N-methyl-p-methoxyphenethylamine and formaldehyde produced via a condensation reaction. It acts as a mast cell degranulator and histamine releaser and inhibits phosphatidylinositol-specific phospholipase C activity in human platelets.

GE1111 is an antagonist of the mas-related G protein-coupled receptor X2 (MRGPRX2), exhibiting an IC50 of 9.42 μM. It inhibits mast cell degranulation with an IC50 of 4.7 μM. In the C48 80-induced systemic allergic reaction model, GE1111 demonstrates both antiallergic and anti-inflammatory properties.

Z-3578 is a small molecule antagonist targeting the MrgX2 (Mas-related G protein-coupled receptor X2) with notable anti-pseudoallergic properties, exhibiting a KD value of 729 nM. It effectively inhibits mast cell degranulation induced by substance P (SP) and C48/80, with IC50 values of 4.90 µM and 6.18 µM, respectively, suppresses the release of β-hexosaminidase, and significantly reduces the release of histamine and TNF-α, as well as intracellular calcium flux. Additionally, in a mouse pseudoallergy model, Z-3578 significantly alleviates foot swelling, dye leakage, and reduces serum histamine levels, indicating a strong in vivo anti-allergic effect. Z-3578 presents as a promising lead compound in the field of anti-allergic treatments, particularly for pseudoallergic reactions.