Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond
Reads0
Chats0
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
Citations
More filters
Journal ArticleDOI
Expression of sphingosine-1-phosphate receptor 2 is correlated with migration and invasion of human colon cancer cells: A preliminary clinical study
TL;DR: A novel mechanism by which S1P inhibited tumour cell migration and invasion via a S1 PR2-dependent pathway is revealed, suggesting that S1PR2 may be a therapeutic target for treatment of colon cancer.
Journal ArticleDOI
Revealing 2-dimethylhydrazino-2-alkyl alkynyl sphingosine derivatives as sphingosine kinase 2 inhibitors: Some hints on the structural basis for selective inhibition.
Macarena Corro-Morón,Albert Granell,Varbina Ivanova,Elena Domingo,Raúl Beltrán-Debón,Xavier Barril,Maria-Jesus Sanz,M. Isabel Matheu,Sergio Castillón,Yolanda Díaz +9 more
TL;DR: In this article , the synthesis of new sphingosine derivatives bearing a tetrasubstituted carbon atom at C-2, dimethylhydrazino or azo moieties in the polar head, and alkane, alkene or alkyne moieties as linkers between the polar ahead and the fatty tail was described.
Journal ArticleDOI
Rational Design, Synthesis, and Biological Evaluation of Novel S1PR2 Antagonists for Reversing 5-FU-Resistance in Colorectal Cancer.
Dong-Dong Luo,Xiaochun Liu,Leilei Jiang,Zhikun Guo,Yan Lv,Xiaochen Tian,Xiaoyan Wang,Shu-Xiang Cui,Shengbiao Wan,Xian-Jun Qu,Ximing Xu,Xiaofang Li +11 more
TL;DR: Novel S1PR2 antagonists based on aryl urea structure designed and synthesized and investigated suggest that 43 could be a novel lead compound for developing a 5-FU resensitizing agent.
References
More filters
Journal ArticleDOI
STATs in cancer inflammation and immunity: a leading role for STAT3
TL;DR: Signal transducer and activator of transcription proteins are central in determining whether immune responses in the tumour microenvironment promote or inhibit cancer, and STAT3 is a promising target to redirect inflammation for cancer therapy.
Journal ArticleDOI
Principles of bioactive lipid signalling: lessons from sphingolipids
TL;DR: An understanding of the complex pathways of sphingolipid metabolism and the mechanisms that regulate lipid generation and lipid action is required to understand the mechanisms of cell growth, death, senescence, adhesion, migration, inflammation, angiogenesis and intracellular trafficking.
Journal ArticleDOI
The many roles of histone deacetylases in development and physiology: Implications for disease and therapy
TL;DR: In this article, the expression of many HDAC isoforms in eukaryotic cells raises questions about their possible specificity or redundancy, and whether they control global or specific programs of gene expression.
Journal Article
Heart-lung transplantation.
TL;DR: A broad overview of the various grounds upon which this difference is likely based and discuss recent advances in each area: 1) criteria for the selection of candidates and donors, 2) methods for ex-vivo preservation of donor organs, 3) technical execution of the operative procedure, and 4) prevention of postoperative infection as discussed by the authors.
Journal ArticleDOI
Mixed Lineage Kinase Domain-like Protein Mediates Necrosis Signaling Downstream of RIP3 Kinase
Liming Sun,Huayi Wang,Zhigao Wang,Sudan He,She Chen,Daohong Liao,Lai Wang,Jiacong Yan,Weilong Liu,Xiaoguang Lei,Xiaodong Wang +10 more
TL;DR: The identification of a small molecule called necrosulfonamide that specifically blocks necrosis downstream of RIP3 activation is reported, which implicate MLKL as a key mediator of necrosis signaling downstream of the kinase RIP3.