Targeting Sphingolipid Metabolism and Signalling in Drug Discovery

Sphingolipids have been linked to many disease conditions, such as inflammation, fibrosis, cancer, autoimmune disease, and cardiovascular disease. Sphingolipids serve as both dynamic structural features in lipid membranes, involved in changes in membrane shape and fluidity, and as important signalling elements. As part of a broader effort in employing Chemical Biology approaches using small-molecules modulators of enzymes and receptors to identify disease targets and drug leads, this thesis mostly focuses on the development of novel and selective small-molecule inhibitors of selected enzymes and receptors in the sphingolipid pathway: dihydroceramide desaturase-1 (Des1) and sphingosine kinases (SK1/2), sphingosine-1-phosphate (S1P) receptor-1 (S1P1 receptor).