Abstract
The conversion of sphingosine to sphingosine-1-phosphate is catalyzed by sphingosine kinase (SphK), which has been implicated in disease states such as cancer and fibrosis. Because SphK exists as two different isoforms, SphK1 and SphK2, understanding the physiological function of each isoenzyme is important. Of the two isoenzymes, SphK2 is significantly less understood, which is evident by the lack of selective small molecule inhibitors. Building on our initial work that focused on the structure-activity relationship study on an FTY720-derived cylohexylamine scaffold, we report that varying the alkyl chain length on the hydrophobic tail can impart selectivity toward SphK2 over SphK1.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Cyclohexylamines / chemistry
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / metabolism
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Fingolimod Hydrochloride
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Isoenzymes / antagonists & inhibitors
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Isoenzymes / metabolism
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Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors*
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Phosphotransferases (Alcohol Group Acceptor) / metabolism
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Propylene Glycols / chemical synthesis
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Propylene Glycols / chemistry*
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Propylene Glycols / metabolism
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Protein Binding
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Sphingosine / analogs & derivatives*
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Sphingosine / chemical synthesis
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Sphingosine / chemistry
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Sphingosine / metabolism
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Structure-Activity Relationship
Substances
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Cyclohexylamines
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Enzyme Inhibitors
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Isoenzymes
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Propylene Glycols
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Phosphotransferases (Alcohol Group Acceptor)
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sphingosine kinase
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Fingolimod Hydrochloride
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Sphingosine