An update on sphingosine-1-phosphate receptor 1 modulators. Issue 23 (15th December 2018)

• Record Type: Journal Article
• Authors: Marciniak, Alexander; Camp, Sara M.; Garcia, Joe G.N.; Polt, Robin
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 23/24(2018)
• Page Start: 3585
• Page End: 3591
• Publication Date: 2018-12-15
• Subjects: Sphingolipids -- Sphingosine-1-phosphate -- Sphingosine-1-phosphate receptor 1 -- Autoimmune modulators -- S1P1 agonists; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2018.10.042
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Sphingolipids represent an essential class of lipids found in all eukaryotes, and strongly influence cellular signal transduction. Autoimmune diseases like asthma and multiple sclerosis (MS) are mediated by the sphingosine-1-phosphate receptor 1 (S1P1 ) to express a variety of symptoms and disease patterns. Inspired by its natural substrate, an array of artificial sphingolipid derivatives has been developed to target this specific G protein-coupled receptor (GPCR) in an attempt to suppress autoimmune disorders. FTY720, also known as fingolimod, is the first oral disease-modifying therapy for MS on the market. In pursuit of improved stability, bioavailability, and efficiency, structural analogues of this initial prodrug have emerged over time. This review covers a brief introduction to the sphingolipid metabolism, the mechanism of action on S1P1, and an updated overview of synthetic sphingosine S1P1 agonists.