BER-5 is a potent MrgX2 antagonist, demonstrating broad-spectrum antagonistic activity against various MrgX2 agonists. It can inhibit Substance P(SP)-induced degranulation in LAD2 cells and alleviate SP-induced allergic reactions in mice. BER-5 is useful for researching mechanisms related to allergic reactions.

BER-5 (12.5-50 μM) specifically inhibits the degranulation reaction in LAD2 cells induced by SP by suppressing the release of β-hexosaminidase (for 30 min), histamine (for 2 h), and IL-8 (for 6 h). BER-5 at a concentration of 0-100 μM over 30 min can inhibit SP-induced release of β-hexosaminidase in LAD2 cells with an IC 50 of 20.64 μM, demonstrating stronger efficacy compared to Bergaptol (BER) (IC 50 = 46.79 μM) and Imperatorin (IMP) (IC 50 = 99.73 μM). Additionally, BER-5 at 50 μM slightly increases the half-maximal effective concentration (EC 50 ) of SP in LAD2 cells while significantly reducing its maximum effect (E max ). Furthermore, BER-5 (12.5-50 μM) inhibits degranulation responses in LAD2 cells induced by the compounds C48/80, (R)-ZINC-3573, Rocuronium Bromide, and Ciprofloxacin, indicating its broad-spectrum antagonistic activity against multiple MrgX2 agonists. Lastly, BER-5 (12.5-50 μM, 30 min) inhibits SP-induced Ca 2+ mobilization in MrgX2-HEK293 cells in a concentration-dependent manner.

The compound BER-5, administered as a single intragastric dose ranging from 6.25 to 25 mg/kg, can alleviate allergic reactions induced by SP in adult mice.