Inhibitors of Glucosylceramide Synthase.

Glucosylceramide synthase can be targeted by high affinity small molecular weight inhibitors for the study of glycosphingolipid metabolism and function or for the treatment of glycosphingolipid storage disorders, including Gaucher and Fabry disease. This work is exemplified by the discovery and development of eliglustat tartrate, the first stand-alone small chemical entity approved for the treatment of Gaucher disease type 1. The development of inhibitors of glucosylceramide synthase that have utility for either research or clinical purposes begins with a testing funnel for screening candidate inhibitors for activity against this enzyme and for activity in lowering the content of glucosylceramide in intact cells. Two common assays for glucosylceramide synthase, one enzyme based and another cell based, are the focus of this chapter.