Prostaglandin D2 receptor 2 (CRTH2) (CRTH2)

Prostaglandin D2 receptor 2 (CRTH2) is a G protein-coupled receptor (GPCR) belonging to the rhodopsin-like family, primarily expressed on Th2 lymphocytes, eosinophils, and basophils [1, 12]. It serves as a high-affinity receptor for prostaglandin D2 (PGD2), a key inflammatory mediator released by mast cells during allergic reactions [7, 14]. Activation of CRTH2 triggers Gi-protein signaling, leading to decreased intracellular cAMP and increased calcium mobilization, which promotes the chemotaxis and activation of these immune cells [1, 11]. This receptor plays a critical role in the pathogenesis of type 2-driven inflammatory diseases, including asthma, allergic rhinitis, and atopic dermatitis [9, 14]. Consequently, CRTH2 has been a major therapeutic target for small-molecule antagonists such as fevipiprant and setipiprant, which aim to block PGD2-mediated recruitment of inflammatory cells to the airways [11, 12]. While these drugs have shown safety and some efficacy in reducing eosinophilic inflammation, several late-stage clinical trials have failed to meet primary endpoints in broad patient populations [12, 15]. This suggests that therapeutic success may depend on biomarker-driven patient selection, particularly for those with a Th2-high phenotype [12]. Beyond allergy, CRTH2 is also being investigated for its roles in other conditions such as eosinophilic pustular folliculitis and potentially certain cancers [7, 8].

Other names

PTGDR2CD294GPR44DL1RDP2

Antagonist