Effect of alkyl chain length on sphingosine kinase 2 selectivity

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:22

Article

Knott, Kenneth¹  Kharel, Yugesh²  Raje, Mithun R.¹  Lynch, Kevin R.²  Santos, Webster L.¹ 

[1] Virginia Tech, Dept Chem, Blacksburg, VA 24061 USA

[2] Univ Virginia, Dept Pharmacol, Charlottesville, VA 22908 USA

关键词: Sphingosine kinase;    Sphingosine;    Cancer;    Structure-activity relationships;    Kinase inhibitors;    FTY720;   

DOI  :  10.1016/j.bmcl.2012.01.050

来源: Elsevier

【 摘 要 】

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. (C) 2012 Elsevier Ltd. All rights reserved.

【 授权许可】

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