Development of ATX and DUSP inhibitors : inhibiting phosphate ester hydrolysis in biology

Abstract

The first part of this thesis describes the development of inhibitors of autotaxin (ATX or ENPP2), a phosphodiesterase that is responsible for the production of the lipid lysophosphatidic acid (LPA) in the circulation. ATX is implicated in several diseases including inflammation, fibrotic disease and cancer, making it an interesting potential drug target to study. ATX inhibitors are required in the validation process of ATX as a drug target. The second part of this thesis describes development of dual specificity phosphatases (DUSP) inhibitors that inhibit bacterial growth in human cells. These inhibitors act by inhibiting DUSP proteins in the host cell that are essential for bacterial growth. This approach can be used to control bacterial infection and could be a useful addition to the current treatment of bacterial infections that target solely the bacteria itself.