HPGDS inhibitor 1

Research use only, not for human use.

A potent, selective, oral hematopoietic prostaglandin D synthase (HPGDS) inhibitor with enzyme IC50 of 0.6 nM.

A potent, selective, oral hematopoietic prostaglandin D synthase (HPGDS) inhibitor with enzyme IC50 of 0.6 nM; does not inhibit human L-PGDS, mPGES, COX-1, COX-2, or 5 LOX (IC50>10 uM); reduces the antigen-induced response in vivo.

HPGDS inhibitor 1 has equal potency against purified HPGDS from human, rat, dog, and sheep (IC50, 0.5-2.3 nM).

HPGDS inhibitor 1 (compound 8; 1 mg/kg) has excellent PK characteristics with 76% bioavailability, and the T1/2 is 4.1 hours in rats.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. HPGDS inhibitor 1 (compound 8; 1 mg/mL) illustrates efficacy in an in vivo sheep model of asthma.

H-PGDS Inhibitor I

Immunology/Inflammation

PGE synthase

hPGDS

Inflammation/Immunology

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1033836-12-2

381.3673

C19H19F4N3O

>98% (HPLC)

10 mM in DMSO

O=C(C1=CC=C(C2=CC=CC(F)=C2)N=C1)NC3CCN(CC(F)(F)F)CC3

3-Pyridinecarboxamide, 6-(3-fluorophenyl)-N-[1-(2,2,2-trifluoroethyl)-4-piperidinyl]-

(-20℃)

With Ice Pack

≥ 2 years