. 2021 Oct 27;10(11):2906. doi: 10.3390/cells10112906

Table 1.

Inhibitors.

Type	Inhibitor	Mechanism	References
Direct inhibition	QWF	Dual action to MRGPRX2 and NK-1 receptor Competitive inhibition of SP binding to MRGPRX2 Inhibition of intracellular Ca²⁺ mobilization and mast cell degranulation Reduction of SP-induced itch	[36]
	Compound 1, 2	MRGPRX2 antagonist, not for NK-1 or M2R Competitive inhibition of SP binding to MRGPRX2 Inhibition of intracellular Ca²⁺ mobilization, ERK signaling, GTP binding, MC degranulation, and de novo PGD₂ production	[32,42]
	Piperine	Direct interaction to MRGPRX2 determined by binding to MRGPRX2-expressing cell membrane Inhibition of intracellular Ca²⁺ mobilization, degranulation, histamine release, cytokines release, PLCγ1, PKC, inositol 1,4,5-triphate receptor, p38, PKB, and ERK Reduction of C48/80-induced anaphylactoid reactions	[141]
	Isoliquiritigenin	Predicted direct interaction to MRGPRX2 Binding to MRGPRX2 by molecular docking assay Inhibition of intracellular Ca²⁺ mobilization, cytokines release, MC degranulation, and histamine release Reduction of C48/80-induced anaphylactoid reactions	[142]
	Shikonin	Direct interaction to MRGPRX2 determined by surface plasmon resonance and molecular docking analysis Inhibition of intracellular Ca²⁺ mobilization, MC degranulation, histamine release, cytokines release, PLCγ1, PKC, inositol 1,4,5-triphate receptor, and ERK Reduction of C48/80-induced anaphylactoid reaction	[143]
	Imperatorin	Direct interaction to MRGPRX2 determined by surface plasmon resonance and molecular docking analysis Inhibition of intracellular Ca²⁺ mobilization, MC degranulation, histamine release, cytokines release, CamKII, and ERK Reduction of SP-induced anaphylactoid reaction and OVA-induced lung inflammtion	[50]
	Roxithromysin	Direct interaction to MRGPRX2 by surface plasmon resonance Inhibition of intracellular Ca²⁺ mobilization, MC degranulation, histamine release, cytokines release, PLCγ1, inositol 1,4,5-triphate receptor, and p38 Reduction of C48/80-induced anaphylactoid reaction	[144]
	Paeoniflorin	Predicted direct interaction to MRGPRX2 Binding to MRGPRX2 by molecular docking analysis Inhibition of intracellular Ca²⁺ mobilization, MC degranulation, histamine release, cytokines release, PLCγ1, inositol 1,4,5-triphate receptor, p38, ERK, AKT, and PKC Reduction of C48/80-induced anaphylactoid reaction	[145]
	Quercetin	Predicted direct interaction to MRGPRX2 Binding to MRGPRX2 by molecular docking analysis Inhibition of intracellular Ca²⁺ mobilization, MC degranulation, histamine release, cytokines release, PLCγ1, inositol 1,4,5-triphate receptor, and ERK Reduction of C48/80-induced anaphylactoid reaction	[146]
	Genistein	Predicted direct interaction to MRGPRX2 Binding to MRGPRX2 by molecular docking analysis Inhibition of intracellular Ca²⁺ mobilization, β-arrestin recruitment, and MC degranulation Reduction of C48/80-induced anaphylactoid reaction	[147]
	Aptamer-X35	ssDNA aptamer Direct interaction to MRGPRX2 determined by binding to MRGPRX2 expressing cells Inhibition of MC degranulation and histamine release Reduction of SP-induced anaphylactoid reaction in MRGPRX2-expressing cell engraft rat	[148]
MRGPRX2 signal inhibitor	Resveratrol	Inhibition of MRGPRX2 downstream signal, NF-κB via Nrf2/HO-1 pathway activation Inhibition of intracellular Ca²⁺ mobilization, MC degranulation, histamine release, and cytokines release Reduction of C48/80-induced anaphylactoid reaction	[149,150]
	Licochalcone A	Inhibition of MRGPRX2 downstream signal, NF-κB Inhibition of intracellular Ca²⁺ mobilization, MC degranulation, and cytokines release Reduction of SP-induced anaphylactoid reaction	[151,152]
	Osthole	Inhibition of MRGPRX2-mediated intracellular Ca²⁺ mobilization, ERK, MC degranulation, and cytokines release Reduction of C48/80-induced paw edema and LL-37-induced inflammation in vivo	[153]
	Dexamethasone	Downregulation of Gαi and MRGPRX2 downstream signals	[154]
	Lactic acid	Inhibition of MRGPRX2-mediated intracellular Ca²⁺ mobilization, MC degranulation, and cytokines release Reduction of LL-37-induced inflammation in vivo	[155]
Others	Ceramide, sphingomyelin	Inhibition of MRGPRX2-mediated mast cell activation by CD300f activation Reduction of MRGPRX2 ligands-induced inflammation in vivo	[156,157]
	ssDNA	Unknown mechanism Reduction of MRGPRX2 ligands-induced inflammation in vivo	[158]
	Sugammadex	Encapsulation of MRGPRX2 ligand Inhibition of intracellular Ca²⁺ mobilization, MC degranulation, and CCL2 release	[159]