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.read more
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References
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TL;DR: In vitro binding assays showed that the implementation of phosphonates as phosphate mimetics provided compounds with similar receptor binding affinities as compared to their phosphate precursors.
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Zhulun Wang,Xiaoshan Min,Shou-Hua Xiao,Sheree Johnstone,William G. Romanow,David Park Meininger,Haoda Xu,Jinsong Liu,Jessica Dai,Songzhu An,Stephen T. Thibault,Nigel Walker +11 more
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Differential Effects of Sphingosine 1–Phosphate Receptors on Airway and Vascular Barrier Function in the Murine Lung
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TL;DR: It is determined that a direct intratracheal or intravenous administration of S1P, or a selective S1PR receptor (S1PR(1)) agonist (SEW-2871), produces highly concentration-dependent barrier-regulatory responses in the murine lung.