Sphingosine-1-phosphate Receptor Modulators in Multiple Sclerosis

Benefit–Risk Profile of Sphingosine-1-Phosphate Receptor Modulators in Relapsing and Secondary Progressive Multiple Sclerosis

Since the approval of fingolimod, several selective sphingosine-1-phosphate receptor modulators have entered clinical development for multiple sclerosis. However, side effects can occur with sphingosine-1-phosphate receptor modulators. By considering short-term data across the drug class and longer term fingolimod data, we aim to highlight the potential of sphingosine-1-phosphate receptor modul...

Sphingosine 1-Phosphate Receptor Modulators and Drug Discovery

Initial discovery on sphingosine 1-phosphate (S1P) as an intracellular second messenger was faced unexpectedly with roles of S1P as a first messenger, which subsequently resulted in cloning of its G protein-coupled receptors, S1P₁₋₅. The molecular identification of S1P receptors opened up a new avenue for pathophysiological research on this lipid mediator. Cellular and molecular in vitro studie...

Sphingosine 1-Phosphate Receptor 1 as a Useful Target for Treatment of Multiple Sclerosis

Sphingosine 1-phosphate (S1P), a lysophospholipid mediator, is generated from sphingosine by sphingosine kinases and binds five known cell surface receptors. S1P receptor 1 (S1P1) plays an essential role in lymphocyte egress from secondary lymphoid organs (SLO), as evinced by the inability of lymphocytes to exit from the SLO in mice lacking lymphocytic S1P1. Fingolimod hydrochloride (FTY720) is...

Fingolimod (FTY720), the Sphingosine 1-Phosphate Receptor Modulator, as a New Therapeutic Drug in Multiple Sclerosis

FTY720 (Fingolimod) is a first-in-class sphingosine 1-phosphate (S1P) receptor modulator that inhibits S1P-dependent lymphocyte egress from secondary lymphoid organs. Oral administration of FTY720 shows a superior efficacy compared to interferon (IFN)-β in relapsing remitting multiple sclerosis (MS), the most common inflammatory disorder of the central nervous system (CNS) and in experimental a...

The Sphingosine 1-Phosphate Receptor