GE1111 is a MRGPRX2 antagonist ( IC50 = 9.4 μM). GE1111 inhibits MRGPRX2 / MRGPRB2 -mediated mast cell activation. GE1111 reduces the expressions of TSLP, IL-13, MCP-1, TNF-α, IL-1β and periostin, maintains the expression levels of claudin 1 and involucrin, restores the phagocytic activity of macrophages, and attenuates the activation of STIM1 and phosphorylated AKT. GE1111 exerts anti-inflammatory and anti-allergic effects in multiple animal models. GE1111 is applicable to the research related to rosacea, atopic dermatitis and ulcerative colitis [1] [2] [3].
In Vivo, GE1111 (10-20 mg/kg; i.p.; daily; 6 days) alleviates LL-37-induced rosacea-like inflammation in mice by inhibiting mast cell degranulation, restoring skin barrier function, and reducing systemic and local inflammatory mediators[1]. GE1111 (20 mg/kg; i.p.; single pre-treatment) alleviates compound 48/80 -induced pruritus in mice by inhibiting mast cell degranulation[1]. GE1111 (10-20 mg/kg; i.p.; weekly; for 4 consecutive weeks) significantly alleviates DNFB-induced atopic dermatitis in mice by reducing skin inflammation, inhibiting mast cell degranulation, downregulating the expression of inflammatory mediators, and restoring the expression of epidermal barrier proteins[2]. GE1111 (300 µg/kg; i.p.; once every other day for 12 days) improves the survival rate of C57BL/6N mice with ulcerative colitis induced by 4% DSS. It alleviates the disease severity of C57BL/6N mice with ulcerative colitis induced by 2.5% DSS by restoring colonic integrity, normalizing cytokine levels, reducing immune cell infiltration, and decreasing the colonic expression of Mrgprb2/Mrgpra1[3].
In Vitro, GE1111 potently inhibits LL-37-induced degranulation of LAD-2 human mast cells, with an IC50 value of 6.271 μM[1]. GE1111 (30 min) inhibits LL-37-induced MRGPRX2-mediated calcium influx in MRGPRX2-transfected HEK-293 cells, with an IC50 of 12.31 μM[1]. GE1111 (50 μM; 30 min) inhibits the activation of LL-37-induced MRGPRX2 downstream signaling pathways (STIM1, ERK 1/2) and reduces the expression of pro-inflammatory cytokine genes (IL-31, MCP-1, TNF-α) in human mast cell line LAD-2[1]. GE1111 (50 μM; 2 h) restores claudin-1 expression, reduces the expression of pro-inflammatory TSLP, and downregulates the expression of pro-inflammatory cytokine genes (IL-8, IL-13, IL-17) in human keratinocyte HaCaT cells exposed to mast cell-conditioned medium[1]. GE1111 (50 μM; 2 h) restores the phagocytic function of RAW 264.7 mouse macrophages impaired by mast cell conditioned medium stimulated with LL-37[1]. GE1111 (0.01 nM-100 μM; 1 h) acts as an inverse agonist and antagonist of MRGPRX2 in Mrgprx2-transfected HTLA cells, reducing both basal β-arrestin recruitment levels and agonist-induced β-arrestin recruitment levels[3]. GE1111 (100 μM; 1 h) induces internalization of MRGPRX2 in LAD2 mast cells[3].
References:
[1]. Chow BKC, et al. Therapeutic effect of an MRGPRX2/MRGPRB2 antagonist on LL-37-induced rosacea-like inflammation in mice. Inflamm Res. 2025;74(1):174. Published 2025 Nov 26.
[2]. Wong TK, et al. MRGPRX2 antagonist GE1111 attenuated DNFB-induced atopic dermatitis in mice by reducing inflammatory cytokines and restoring skin integrity. Front Immunol. 2024;15:1406438. Published 2024 May 16.
[3]. Duraisamy K, et al. MRGPRB2/X2 and the analogous effects of its agonist and antagonist in DSS-induced colitis in mice. Biomed Pharmacother. 2024;174:116471.
In Vivo, GE1111 (10-20 mg/kg; i.p.; daily; 6 days) alleviates LL-37-induced rosacea-like inflammation in mice by inhibiting mast cell degranulation, restoring skin barrier function, and reducing systemic and local inflammatory mediators[1]. GE1111 (20 mg/kg; i.p.; single pre-treatment) alleviates compound 48/80 -induced pruritus in mice by inhibiting mast cell degranulation[1]. GE1111 (10-20 mg/kg; i.p.; weekly; for 4 consecutive weeks) significantly alleviates DNFB-induced atopic dermatitis in mice by reducing skin inflammation, inhibiting mast cell degranulation, downregulating the expression of inflammatory mediators, and restoring the expression of epidermal barrier proteins[2]. GE1111 (300 µg/kg; i.p.; once every other day for 12 days) improves the survival rate of C57BL/6N mice with ulcerative colitis induced by 4% DSS. It alleviates the disease severity of C57BL/6N mice with ulcerative colitis induced by 2.5% DSS by restoring colonic integrity, normalizing cytokine levels, reducing immune cell infiltration, and decreasing the colonic expression of Mrgprb2/Mrgpra1[3].
In Vitro, GE1111 potently inhibits LL-37-induced degranulation of LAD-2 human mast cells, with an IC50 value of 6.271 μM[1]. GE1111 (30 min) inhibits LL-37-induced MRGPRX2-mediated calcium influx in MRGPRX2-transfected HEK-293 cells, with an IC50 of 12.31 μM[1]. GE1111 (50 μM; 30 min) inhibits the activation of LL-37-induced MRGPRX2 downstream signaling pathways (STIM1, ERK 1/2) and reduces the expression of pro-inflammatory cytokine genes (IL-31, MCP-1, TNF-α) in human mast cell line LAD-2[1]. GE1111 (50 μM; 2 h) restores claudin-1 expression, reduces the expression of pro-inflammatory TSLP, and downregulates the expression of pro-inflammatory cytokine genes (IL-8, IL-13, IL-17) in human keratinocyte HaCaT cells exposed to mast cell-conditioned medium[1]. GE1111 (50 μM; 2 h) restores the phagocytic function of RAW 264.7 mouse macrophages impaired by mast cell conditioned medium stimulated with LL-37[1]. GE1111 (0.01 nM-100 μM; 1 h) acts as an inverse agonist and antagonist of MRGPRX2 in Mrgprx2-transfected HTLA cells, reducing both basal β-arrestin recruitment levels and agonist-induced β-arrestin recruitment levels[3]. GE1111 (100 μM; 1 h) induces internalization of MRGPRX2 in LAD2 mast cells[3].
References:
[1]. Chow BKC, et al. Therapeutic effect of an MRGPRX2/MRGPRB2 antagonist on LL-37-induced rosacea-like inflammation in mice. Inflamm Res. 2025;74(1):174. Published 2025 Nov 26.
[2]. Wong TK, et al. MRGPRX2 antagonist GE1111 attenuated DNFB-induced atopic dermatitis in mice by reducing inflammatory cytokines and restoring skin integrity. Front Immunol. 2024;15:1406438. Published 2024 May 16.
[3]. Duraisamy K, et al. MRGPRB2/X2 and the analogous effects of its agonist and antagonist in DSS-induced colitis in mice. Biomed Pharmacother. 2024;174:116471.