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“1 Fossariinae Introduction Setipiprant (ACT-129968, 2-(2-(1-naphthoyl)-8-fluoro-3,4-dihydro-1H-pyrido[4,3-b]APR-246 mw indol-5(2H)-yl)acetic acid) is an orally available, selective CRTH2 (chemoattractant receptor-homologous molecule expressed on T helper [Th]-2 cells) antagonist. CRTH2 is a G protein-coupled receptor for prostaglandin (PGD2). PGD2 is produced by the mast cells and is a key mediator in various inflammatory diseases,
including allergy and asthma [1–3]. Binding of PGD2 to CRTH2, which are expressed on the surface of blood-borne cells, induces chemotaxis of Th2 cells, basophils, and eosinophils, and stimulates cytokine release from these cells [2, 4]. Thus, antagonism of CRTH2 receptors is considered to be a promising therapeutic target for various allergic diseases and asthma. Preclinical data showed that setipiprant potently inhibits migration of eosinophils towards PGD2 in vitro as well as in an in vivo rat model of lung eosinophilia (Actelion Pharmaceuticals Ltd, data on file). In the entry-into-man study in healthy male subjects, single and multiple doses of setipiprant of up to 1,000 mg twice daily (bid) for 6 days showed excellent tolerability and a favorable pharmacokinetic profile (Sidharta et al., unpublished data). The pharmacokinetics of setipiprant were characterized by a rapid absorption with a time to maximum plasma concentration (t max) of 2–4 h, followed by a biphasic elimination pattern.