AT-56 is an orally active, selective inhibitor of lipocalin-type prostaglandin D synthase (L-PGDS) with Ki of 75 uM, IC50 of 95 uM.
AT-56 inhibited the L-PGDS activity in a competitive manner against the substrate PGH2 (Km = 14 μM) with a Ki value of 75 μM but did not inhibit the binding of 13-cis-retinoic acid, a nonsubstrate lipophilic ligand, to L-PGDS.
AT-56 occupied the catalytic pocket, but not the retinoid-binding pocket, of L-PGDS.
AT-56 inhibited the production of PGD2 by L-PGDS-expressing human TE-671 cells after stimulation with Ca2+ ionophore (5 μm A23187) with an IC50 value of 3 uM.
Orally administered AT-56 (<30 mg/kg body weight) decreased the PGD2 production to 40% in the brain of H-PGDS-deficient mice, without affecting the production of PGE2 and PGF2α.
AT-56 also suppressed the accumulation of eosinophils and monocytes in the bronco-alveolar lavage fluid from the antigen-induced lung inflammation model of human L-PGDS-transgenic mice.