Identification of Direct Intracellular Targets of Sphingosine 1‐Phosphate (S1P)

Hait, Nitai C.; Milstien, Sheldon; Spiegel, Sarah

doi:10.1002/9781118531426.ch4

Cited by 1 publication

(1 citation statement)

References 31 publications

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“…These discoveries were made possible by advances in biotechnology, and have revealed that S1P plays a role in mitochondrial function and assembly; affects gene expression by inhibiting histone deacetylases 1 and 2 (HDAC1 and 2); and acts as a cofactor for TRAF2 (TNF receptor--associated factor 2), which ultimately suppresses apoptosis. 46 While S1P is an essential player in the homeostasis of all eukaryotes, aberrant S1P signaling has been implicated in many different diseases. 47 Particularly, S1P has been shown to be an important contributor to the progression and onset of cancer.…”

Section: Apoptosis / Senesencementioning

confidence: 99%

Pharmacological Targeting of Sphingosine Kinase: Conventional, Bisubstrate, and Irreversible Inhibitors

Dawson¹

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Cancer is rapidly becoming the world's greatest health problem, and current treatments are often harsh and ineffective. The demand for improved modes of therapy has fueled research in recent decades and led to a deeper, more fundamental understanding of cancer biology. Today, drug discoverers exploit knowledge of tumor growth and stress-support pathways to develop therapeutics with novel mechanisms of action, greater selectivity for cancer cells, lower toxicity, and, theoretically, greater efficacy. A particularly attractive target for new cancer drugs is the sphingolipid signaling pathway. Cellular levels of the lipids ceramide, sphingosine, and sphingosine 1-phosphate (S1P) are strictly regulated by various enzymes, and play a large role in determining cellular growth and fate. Specifically, S1P has emerged as a driver of processes such as cell growth, proliferation, inflammation, resistance to apoptosis, and angiogenesis, and has been implicated in nearly every type of cancer. Thus, biomolecular agents that affect levels of S1P may be viable as targeted cancer therapies or for the treatment of hyperproliferative and inflammatory diseases. As the sole producers of physiological S1P, the two sphingosine kinases (SphK1 and SphK2) have been the subject of intense investigation during the last decade. Many inhibitors of the SphKs have been discovered, and have proven to be effective pharmacological probes of these kinases. However, significant improvements in the potency, SphK-subtype selectivity, and pharmacokinetic properties of SphK inhibitors

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Section: Apoptosis / Senesencementioning

confidence: 99%

Pharmacological Targeting of Sphingosine Kinase: Conventional, Bisubstrate, and Irreversible Inhibitors

Dawson¹

View full text Add to dashboard Cite

show abstract

Identification of Direct Intracellular Targets of Sphingosine 1‐Phosphate (S1P)

Cited by 1 publication

References 31 publications

Pharmacological Targeting of Sphingosine Kinase: Conventional, Bisubstrate, and Irreversible Inhibitors

Pharmacological Targeting of Sphingosine Kinase: Conventional, Bisubstrate, and Irreversible Inhibitors

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