Hematopoietic prostaglandin D2 synthase (H-PGDS)

Hematopoietic prostaglandin D2 synthase (H-PGDS) is a sigma-class glutathione S-transferase enzyme that catalyzes the conversion of prostaglandin H2 into prostaglandin D2 (PGD2) (UniProt: P51784). It is primarily expressed in immune cells such as mast cells, Th2 cells, and dendritic cells, where it serves as a critical driver of allergic and inflammatory responses (PubMed: 11113130). Unlike the lipocalin-type PGD synthase found in the central nervous system, H-PGDS is the dominant source of PGD2 in peripheral tissues during inflammatory events. Elevated H-PGDS activity is associated with the pathogenesis of asthma, allergic rhinitis, and Duchenne muscular dystrophy (DMD), where PGD2 exacerbates tissue damage and hinders repair (PubMed: 28838915). Pharmacological inhibition of H-PGDS, using small molecules like TAS-204, aims to reduce PGD2-mediated inflammation without interfering with the production of other essential prostanoids like prostacyclin or thromboxane (PubMed: 30104248). This selectivity offers a potential advantage over traditional non-steroidal anti-inflammatory drugs (NSAIDs) for treating chronic inflammatory and degenerative conditions.

Other names

HPGDSGlutathione-dependent PGD synthaseHematopoietic-type prostaglandin D synthaseGSTS1PGD2 synthaseSigma-class glutathione S-transferase

Selective inhibition of the H-PGDS enzyme to prevent the synthesis of pro-inflammatory prostaglandin D2 from prostaglandin H2.