Sphingosine kinases as druggable targets

Pyne, Susan and Adams, David R. and Pyne, Nigel J.; Gomez-Cambronero, Julian and Frohman, Michael A., eds. (2020) Sphingosine kinases as druggable targets. In: Lipid Signaling in Human Diseases. Springer Berlin Heidelberg, Cham, Switzerland, pp. 49-76. ISBN 978-3-030-33668-4

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    Abstract

    There is substantial evidence that the enzymes, sphingosine kinase 1 and 2, which catalyse the formation of the bioactive lipid, sphingosine 1-phosphate are involved in physiological and pathophysiological processes. In this chapter, we appraise the evidence that both enzymes are druggable and describe how isoform-specific inhibitors can be developed based on the plasticity of the sphingosine-binding site. This is contextualised with the effect of sphingosine kinase inhibitors in cancer, pulmonary hypertension, neurodegeneration, inflammation and sickling.