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Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond

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TLDR
The ways in which S1P might be therapeutically targeted are discussed — for example, via the development of chemical inhibitors that target the generation, transport and degradation of S 1P and via thedevelopment of specific S1p receptor agonists.
Abstract
The bioactive lipid sphingosine-1-phosphate (S1P) is involved in multiple cellular signalling systems and has a pivotal role in the control of immune cell trafficking. As such, S1P has been implicated in disorders such as cancer and inflammatory diseases. This Review discusses the ways in which S1P might be therapeutically targeted — for example, via the development of chemical inhibitors that target the generation, transport and degradation of S1P and via the development of specific S1P receptor agonists. We also highlight recent conflicting results observed in preclinical studies targeting S1P and discuss ongoing clinical trials in this field.

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The Concise Guide to PHARMACOLOGY 2013/14: Enzymes

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STAT3 Target Genes Relevant to Human Cancers

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References
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Journal ArticleDOI

Design and Synthesis of Selective and Potent Orally Active S1P5 Agonists

TL;DR: The studies of various benzamide modifications carried out to improve the selectivity, bioactivity, pharmacokinetic properties, and ancillary profile of 1 are reported, ultimately resulting in the discovery of potent and very selective S1P5 agonists.
Journal ArticleDOI

SAR Analysis of Innovative Selective Small Molecule Antagonists of Sphingosine-1-Phosphate 4 (S1P4) Receptor

TL;DR: By expanding the molecular diversity within the hit-derived class, the SAR study provides innovative small molecule potent and selective S1P(4) antagonists suitable for in vivo pharmacological validation of the target receptor.
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Prevention of GVHD and graft rejection by a new S1P receptor agonist, W-061, in rat small bowel transplantation

TL;DR: Data suggest that W-061 has considerable potential as a new therapeutic immunosuppressant in patients with small bowel transplantation (SBTx), as seen histopathologically in comparison with untreated control rats.
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