Hematopoietic Prostaglandin D Synthase (HPGDS) is responsible for the synthesis of PGD2 (Prostaglandin D2), a mediator of allergy and inflammation, by mast cells and Th-2 cells. HPGDS inhibitor 1 is a potent and selective HPGDS inhibitor with IC50s of 0.6 nM and 32 nM in enzyme and cell-based assays, respectively. In vitro, HPGDS inhibitor 1 had equal potency against purified HPGDS from human, rat, dog, and sheep (IC50, 0.5-2.3 nM). Oral administration of HPGDS inhibitor 1 (1 mg/kg and 10 mg/kg) blocked PGD2 production in the rat spleen in a time- and dose-dependent manner. Moreover, HPGDS inhibitor 1 (1 mg/mL) illustrated efficacy in a sheep model of asthma[2].
作用机制
There is a favorable π-π stacking interaction between the central pyridyl ring of the compound and the Trp104 of the protein[2].
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