Inhibitors of Glucosylceramide Synthase

James A Shayman; Vania Hinkovska-Galcheva; Liming Shu

doi:10.1007/978-1-0716-2910-9_20

Inhibitors of Glucosylceramide Synthase

Methods Mol Biol. 2023:2613:271-288. doi: 10.1007/978-1-0716-2910-9_20.

Authors

James A Shayman¹, Vania Hinkovska-Galcheva², Liming Shu³

Affiliations

¹ Departments of Internal Medicine and Pharmacology, University of Michigan Medical School, Ann Arbor, MI, USA. jshayman@med.umich.edu.
² University of Michigan Medical School, Ann Arbor, MI, USA.
³ Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.

PMID: 36587085
DOI: 10.1007/978-1-0716-2910-9_20

Abstract

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.

Keywords: Ceramide; Eliglustat tartrate; Gaucher disease; Glucosylceramide synthase; UDP-glucose.

MeSH terms

Enzyme Inhibitors / pharmacology
Enzyme Inhibitors / therapeutic use
Gaucher Disease* / drug therapy
Gaucher Disease* / metabolism
Glucosylceramides
Glucosyltransferases / metabolism
Glycosphingolipids
Humans

Substances

ceramide glucosyltransferase
Glucosyltransferases
Glucosylceramides
Glycosphingolipids
Enzyme Inhibitors