2. Academic Validation
  3. An update on sphingosine-1-phosphate receptor 1 modulators

An update on sphingosine-1-phosphate receptor 1 modulators

  • Bioorg Med Chem Lett. 2018 Dec 15;28(23-24):3585-3591. doi: 10.1016/j.bmcl.2018.10.042.
Alexander Marciniak 1,  Sara M Camp 2,  Joe G N Garcia 3,  Robin Polt 4
Affiliations

Affiliations

  • 1 Department of Chemistry & Biochemistry, The University of Arizona, Tucson, AZ 85721, United States. Electronic address: [email protected].
  • 2 Department of Medicine, The University of Arizona, Tucson, AZ 85724, United States. Electronic address: [email protected].
  • 3 Department of Medicine, The University of Arizona, Tucson, AZ 85724, United States. Electronic address: [email protected].
  • 4 Department of Chemistry & Biochemistry, The University of Arizona, Tucson, AZ 85721, United States. Electronic address: [email protected].
PMID: 30409535 DOI: 10.1016/j.bmcl.2018.10.042
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.

Keywords

Autoimmune modulators; S1P(1) agonists; Sphingolipids; Sphingosine-1-phosphate; Sphingosine-1-phosphate receptor 1.

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