Novel Agents Targeting Sphingolipid Signalling

This thesis explores the sphingolipid pathway as a novel area of therapy in the treatment of cancer, fibrosis and multiple sclerosis. In a scaffold-hopping approach we have developed a compound library of drug-like non-lipid sphingolipid mimetics with improved phenotypic, physicochemical and pharmacokinetic activity relative to current frontrunners, as part of an ongoing optimisation effort. Our compounds further demonstrate a unique mechanism of action, which overcomes pathway redundancy of contemporary kinase inhibitors and receptor antagonists through phosphatase activation. As well as focusing on the development of viable drug candidates, this work further investigates the structure-activity relationship of our compounds in connection to activity.