Hematopoietic prostaglandin D synthase (H-PGDS) (H-PGDS)

Hematopoietic prostaglandin D synthase (H-PGDS), also known as sigma-class glutathione S-transferase (GSTS1), is a key enzyme responsible for the production of prostaglandin D2 (PGD2), a major mediator of inflammation and allergic reactions (UniProt P51784). While most glutathione S-transferases are involved in the detoxification of xenobiotics, H-PGDS is unique as the only sigma-class member in mammals and functions primarily as an isomerase in the arachidonic acid cascade (PubMed: 11481253). It is highly expressed in mast cells, Th2 cells, and macrophages, where it converts prostaglandin H2 into PGD2 in a glutathione-dependent manner. PGD2 signaling through its receptors (DP1 and CRTH2) promotes vasodilation, bronchoconstriction, and the recruitment of inflammatory cells, linking H-PGDS to the pathogenesis of asthma and allergic rhinitis (PubMed: 22461446). Additionally, H-PGDS has been identified as a therapeutic target in Duchenne muscular dystrophy (DMD), as PGD2-mediated inflammation exacerbates muscle necrosis (PubMed: 25660366). Pharmacological inhibition of H-PGDS, using small molecules like TAS-204, aims to reduce PGD2 levels to treat inflammatory and degenerative conditions without the side effects associated with broader COX inhibitors.

Other names

GSTS1GSTS1-1Glutathione S-transferase sigma 1PGD2 synthaseHematopoietic-type PGD synthase

Selective inhibition of the hematopoietic prostaglandin D synthase enzyme to prevent the conversion of PGH2 to PGD2.