HPGDS inhibitor 1

HPGDS inhibitor 1 is a potent, selective and orally active Hematopoietic Prostaglandin D Synthase (HPGDS) inhibitor with an IC₅₀s of 0.6 nM and 32 nM in enzyme and cellular assays, respectively. HPGDS inhibitor 1 does not inhibit human L-PGDS, mPGES, COX-1, COX-2, or 5-LOX^[1]. IC50 & Target: IC50: 0.6 nM (HPGDS in enzyme assays) and 32 nM (HPGDS in cellular assays)^[1] In Vitro: HPGDS inhibitor 1 has equal potency against purified HPGDS from human, rat, dog, and sheep (IC₅₀, 0.5-2.3 nM)^[1]. In Vivo: HPGDS inhibitor 1 (compound 8; 1 mg/kg) has excellent PK characteristics with 76% bioavailability, and the T_1/2 is 4.1 hours in rats^[1].
Rats dosed orally with 1 mg/kg and 10 mg/kg HPGDS inhibitor 1 (compound 8) are sacrificed at various times. Oral administration of HPGDS inhibitor 1 blocks PGD2 production in the rat spleen; inhibition of PGD2 is inversely correlated with the plasma concentration of HPGDS inhibitor 1 in a time- and dose-dependent manner^[1].
HPGDS inhibitor 1 (compound 8; 1 mg/mL) illustrates efficacy in an in vivo sheep model of asthma^[1].