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Autotaxin (ATX) is a circulating enzyme that plays a major role in the production of lysophosphatic acid (LPA) species in blood. A role for ATX–LPA signalling has been described in multiple disease areas, in particular fibrosis. The involvement of the ATX–LPA axis in fibrosis is based on clinical observations in patients as well as characterization of ATX–LPA regulation, genetic deletion and effects of ATX inhibitors or LPA antagonists in preclinical models of fibrosis in rodents. The three dimensional structure of ATX revealed several possible binding modes for inhibitors which might affect ATX activity beyond LPA production. This chapter describes the role of ATX in fibrotic diseases and the properties of ATX inhibitors that have been evaluated in rodent models of lung, liver or skin fibrosis. A description of ATX inhibitors in clinical use or progressing towards entering clinical trials based on literature, patent applications and press releases from actors in the field is also included.

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