AT 56

PGD24 is a lipid mediator involved in sleep and inflammatory responses. PGD2 activates two different types of receptors. PGD2 regulates sleep and pain via DP1 receptors in the central nervous system. This prostanoid also causes contraction of airway smooth muscle via DP1 receptors and mediates chemotaxis of eosinophils and basophils into the lung via DP2 receptors in the periphery. Therefore, PGD2 coordinately regulates allergic reactions, especially airway inflammation, via these two receptors. AT-56 is an orally active and selective inhibitor of lipocalin-type prostaglandin D synthase.

In vitro: AT-56 inhibited human and mouse L-PGDSs in a concentration (3-250 μM)-dependently but did not affect the activities of hematopoietic PGD synthase (H-PGDS), cyclooxygenase-1 and -2, and microsomal PGE synthase-1. AT-56 inhibited 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. [2].

In vivo: Orally administered AT-56 (

Clinical trial: Up to now, AT-56 is still in the preclinical development stage.

Reference:
[1] Daisuke Irikura, Kosuke Aritake, Nanae Nagata, Toshihiko Maruyama, Shigeru Shimamoto, and Yoshihiro Urade.  Biochemical, Functional, and Pharmacological Characterization of AT-56, an Orally Active and Selective Inhibitor of Lipocalin-type Prostaglandin D Synthase. J Biol Chem. 2009 Mar 20;284(12):7623-30.