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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Sphingosine-1-Phosphate Receptor-2 Antagonists: Therapeutic Potential and Potential Risks
TL;DR: The present review will focus on the therapeutic potential of S1P2 receptor antagonists and discuss their opportunities as well as their potential risks.
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Site-Selective γ-C(sp3 )-H and γ-C(sp2 )-H Arylation of Free Amino Esters Promoted by a Catalytic Transient Directing Group.
TL;DR: A variety of free amino esters, including α-amino esters and β-aminos, amino monoesters and amino bis-esters, are shown to react with a diverse range of simple aryl and heteroaryl iodide reagents.
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ABCC1-Exported Sphingosine-1-phosphate, Produced by Sphingosine Kinase 1, Shortens Survival of Mice and Patients with Breast Cancer.
Akimitsu Yamada,Masayuki Nagahashi,Masayuki Nagahashi,Tomoyoshi Aoyagi,Wei-Ching Huang,Wei-Ching Huang,Santiago Lima,Nitai C. Hait,Nitai C. Hait,Aparna Maiti,Kumiko Kida,Kumiko Kida,Krista P. Terracina,Hiroshi Miyazaki,Takashi Ishikawa,Itaru Endo,Michael R. Waters,Qianya Qi,Li Yan,Sheldon Milstien,Sarah Spiegel,Kazuaki Takabe +21 more
TL;DR: It is demonstrated that high expression of ABCC1, but not ABCB1, is associated with poor prognosis in breast cancer patients and export of S1P viaABCC1 functions in a malicious feed-forward manner to amplify the S1p axis involved in breast cancers progression and metastasis, which has important implications for prognosis of breast cancers patients and for potential therapeutic targets.
Journal ArticleDOI
Sphingosine 1-Phosphate Produced by Sphingosine Kinase 2 Intrinsically Controls Platelet Aggregation In Vitro and In Vivo
Nicole Urtz,Florian Gaertner,Marie-Luise von Bruehl,Sue Chandraratne,Faridun Rahimi,Lingli Zhang,Mathias Orban,Verena Barocke,Johannes Beil,Irene Schubert,Michael Lorenz,Kyle R. Legate,Andrea Huwiler,Josef Pfeilschifter,Christian Beerli,David Ledieu,Elke Persohn,Andreas Billich,Thomas Baumruker,Michael Mederos y Schnitzler,Steffen Massberg +20 more
TL;DR: It is demonstrated that Sphk2 is the major Sphk isoform responsible for the generation of S1P in platelets and plays a pivotal intrinsic role in the control of platelet activation.
Journal ArticleDOI
SPHK1 is a novel target of metformin in ovarian cancer
Peter C. Hart,Tatsuyuki Chiyoda,Tatsuyuki Chiyoda,Xiaojing Liu,Melanie Weigert,Marion Curtis,Chun-Yi Chiang,Rachel M. Loth,Ricardo R. Lastra,Stephanie M. McGregor,Stephanie M. McGregor,Jason W. Locasale,Ernst Lengyel,Iris L. Romero +13 more
TL;DR: It was found that ovarian cancer patients taking metformin had significantly reduced serum S1P levels, a finding that was recapitulated when ovarian cancer cells were treated with meetformin and analyzed by lipidomics, which suggested that in cancer the sphingolipid rheostat may be a novel metabolic target of met formin.
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