An update on sphingosine-1-phosphate receptor 1 modulators

Alexander Marciniak, Sara M. Camp, Joe GN Garcia, Robin L Polt

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalBioorganic and Medicinal Chemistry Letters
DOIs
StateAccepted/In press - Jan 1 2018

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Lysosphingolipid Receptors
Sphingolipids
Modulators
Multiple Sclerosis
Mouth Diseases
Signal transduction
Sphingosine
Prodrugs
G-Protein-Coupled Receptors
Eukaryota
Metabolism
Biological Availability
Autoimmune Diseases
Signal Transduction
Asthma
Derivatives
Lipids
Substrates
Fingolimod Hydrochloride
Therapeutics

Keywords

  • Autoimmune modulators
  • S1P agonists
  • Sphingolipids
  • Sphingosine-1-phosphate
  • Sphingosine-1-phosphate receptor 1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

An update on sphingosine-1-phosphate receptor 1 modulators. / Marciniak, Alexander; Camp, Sara M.; Garcia, Joe GN; Polt, Robin L.

In: Bioorganic and Medicinal Chemistry Letters, 01.01.2018.

Research output: Contribution to journalArticle

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