Prostaglandin DP2 receptor (DP2)

The Prostaglandin DP2 receptor, also known as CRTH2 (Chemoattractant receptor-homologous molecule expressed on Th2 cells), is a G protein-coupled receptor (GPCR) that plays a pivotal role in mediating allergic inflammation (UniProt: Q9Y5Y4). It is primarily expressed on Th2 lymphocytes, eosinophils, and basophils, where it responds to prostaglandin D2 (PGD2) released by mast cells during an allergic response (NCBI Gene: 11251). Activation of DP2 triggers the recruitment and activation of these immune cells, leading to the production of pro-inflammatory cytokines like IL-4, IL-5, and IL-13 (PMID: 27534614). Because of its central role in the Th2-driven inflammatory cascade, DP2 has been extensively targeted for the treatment of asthma, allergic rhinitis, and atopic dermatitis (PMID: 31843464). Small-molecule antagonists such as fevipiprant and setipiprant were developed to block PGD2 binding, aiming to reduce airway eosinophilia and improve lung function (PubChem: Prostaglandin D2 receptor 2). However, several high-profile clinical trials, including those for fevipiprant, failed to meet primary endpoints in broad asthma populations, raising questions about the target's efficacy in non-selected patients (PMID: 32330403). Despite these challenges, the receptor remains a significant focus for research into precision medicine for severe eosinophilic asthma endotypes.

Other names

CRTH2Chemoattractant receptor-homologous molecule expressed on Th2 cellsGPR44G protein-coupled receptor 44CD294Prostaglandin D2 receptor 2

Competitive antagonism of the prostaglandin D2 receptor to inhibit Gi-protein mediated signaling and prevent the recruitment and activation of Th2 cells, eosinophils, and basophils (PMID: 27534614).