Antagonists of the prostaglandin D2 receptor CRTH2.

Prostaglandin D(2) (PGD(2)) is produced by mast cells, Th2 lymphocytes and dendritic cells and causes activation of Th2 lymphocytes, eosinophils and basophils through a high-affinity interaction with the G protein-coupled receptor chemoattractant homologous receptor expressed on Th2 cells (CRTH2, also known as DP(2)). Activation of CRTH2 induces chemotaxis of Th2 lymphocytes and eosinophils and has the unusual property of promoting cytokine production by Th2 lymphocytes in the absence of allergen or co-stimulation. The ability of supernatants from immunologically activated mast cells to activate Th2 cells and eosinophils is mediated by CRTH2. This receptor also plays an important role in amplifying allergic responses through paracrine activation of Th2 cells. Pharmacological blockade or genetic ablation of CRTH2 is associated with a reduction in airways inflammation and reduced levels of mucus, Th2 cytokines and immunoglobulin E. The central role played by CRTH2 in mediating these effects suggests that antagonism of this receptor is an attractive approach to the treatment of chronic allergic disease.

Pettipher R ，Hansel TT 《drug news & perspectives》

Pharmacologic profile of OC000459, a potent, selective, and orally active D prostanoid receptor 2 antagonist that inhibits mast cell-dependent activation of T helper 2 lymphocytes and eosinophils.

Pettipher R ，Vinall SL ，Xue L ，Speight G ，Townsend ER ，Gazi L ，Whelan CJ ，Armer RE ，Payton MA ，Hunter MG ... -  《-》

CRTH2 mediates the activation of human Th2 cells in response to PGD(2) released from IgE/anti-IgE treated nasal polyp tissue.

Pérez-Novo CA ，Holtappels G ，Vinall SL ，Xue L ，Zhang N ，Bachert C ，Pettipher R ... -  《-》

CRTH2 and D-type prostanoid receptor antagonists as novel therapeutic agents for inflammatory diseases.

Schuligoi R ，Sturm E ，Luschnig P ，Konya V ，Philipose S ，Sedej M ，Waldhoer M ，Peskar BA ，Heinemann A ... -  《-》

Differential modulation of human basophil functions through prostaglandin D2 receptors DP and chemoattractant receptor-homologous molecule expressed on Th2 cells/DP2.

Yoshimura-Uchiyama C ，Iikura M ，Yamaguchi M ，Nagase H ，Ishii A ，Matsushima K ，Yamamoto K ，Shichijo M ，Bacon KB ，Hirai K ... -  《CLINICAL AND EXPERIMENTAL ALLERGY》