Prostaglandin D2 receptor 2 (DP2) (DP2)

Prostaglandin D2 receptor 2 (DP2), commonly referred to as CRTH2 (Chemoattractant receptor-homologous molecule expressed on Th2 cells), is a G protein-coupled receptor that plays a pivotal role in the type 2 immune response (UniProt P44597). It is predominantly expressed on Th2 cells, eosinophils, and basophils, where it mediates the pro-inflammatory effects of prostaglandin D2 (PGD2) released by mast cells (PubMed: 11359911). Activation of DP2 promotes the chemotaxis and activation of these cells, contributing significantly to the pathogenesis of allergic conditions such as asthma, allergic rhinitis, and atopic dermatitis (PubMed: 29108867). As a therapeutic target, DP2 has been the focus of numerous drug development programs aiming to treat eosinophilic inflammation. Small molecule antagonists like fevipiprant and setipiprant were designed to block PGD2-mediated signaling, thereby reducing airway inflammation and improving lung function (PubMed: 31864981). Despite promising early-phase results, several high-profile DP2 antagonists failed to meet primary endpoints in Phase 3 clinical trials, leading to a re-evaluation of the target's utility in broad versus specific patient endotypes (PubMed: 32330448).

Other names

CRTH2Chemoattractant receptor-homologous molecule expressed on Th2 cellsGPR44CD294PTGDR2G protein-coupled receptor 44DL1R

Antagonism of the DP2 receptor to inhibit prostaglandin D2-mediated recruitment and activation of Th2 cells, eosinophils, and basophils, thereby reducing type 2 cytokine production and allergic inflammation.