Biological Activity
AT-56 is a potent, selective and orally active inhibitor of lipocalin-type prostaglandin D synthase (L-PGDS), with an IC50 of 95 μM and Ki of 75 μM. AT-56 could selectively suppress the drowsiness or pain reaction mediated by L-PGDS-catalyzed PGD2[1].
In Vitro
AT-56 (1-30 μM; 10 minutes) dose-dependently inhibits the production of PGD2 in L-PGDS-expressing human medulloblastoma TE-671 cells with an IC50 of about 3 μM[1].
In Vivo
AT-56 ( 1-30 mg/kg; p.o.) suppresses the PGD2 production in the stab-wounded brain[1]. AT-56 (1-10 mg/kg; p.o.) suppresses the L-PGDS-mediated allergic airway inflammation in mice[1]. AT-56 (10 mg/kg; p.o.) exhibits Cmax (2.15 μg/ml), half-life (1.71 h) and high oral bioavailability (82%)[1]. Animal Model: H-PGDS KO mice (14-16weeks, 25-30 g, C57BL/6 strain) with a stab wound brain injury[1] Dosage: 0, 1, 3, 10, 30 mg/kg Administration: P.o. 1 h before the stab wound injury Result: Inhibited the L-PGDS reaction in the brain. Decreased the total amount of PGD2 in the brain to 40% with 30 mg/kg AT-56. Animal Model: Human L-PGDS-overexpressing TG mice (males, 14-16 weeks, 25-30 g)[1] Dosage: 0, 1, 10 mg/kg Administration: P.o. 1 h before and 24 h after the antigen exposure Result: Prevented the eosinophil infiltration by inhibiting transgened human L-PGDS. Animal Model: Male C57BL/6 mice (7 weeks, 22-26 g)[1] Dosage: 10 mg/kg for p.o. and 2 mg/kg for i.v. (Pharmacokinetic Analysis) Administration: P.o. and i.v. administration Result: Oral bioavailability (82%); Cmax (2.15 μg/ml); T1/2 (1.71 h, p.o.); T1/2 (2.35 h, i.v.).
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.