Importance of sphingosine kinase (SphK) as a target in developing cancer therapeutics and recent developments in the synthesis of novel SphK inhibitors

Sphingosine kinase (SphK) is an oncogenic lipid kinase that regulates the sphingolipid metabolic pathway that has been shown to play a role in numerous hyperproliferative/inflammatory diseases. The SphK isoforms (SphK1 and SphK2) catalyze the conversion of the proapoptotic substrate d-erythrosphingo...

Full description

Saved in:
Bibliographic Details
Published in:Journal of medicinal chemistry 2014-07, Vol.57 (13), p.5509-5524
Main Authors: Plano, Daniel, Amin, Shantu, Sharma, Arun K
Format: Article
Language:English
Subjects:
Clofibrate - metabolism
Drug Combinations
Enzyme Inhibitors - chemical synthesis
Humans
Isoenzymes - metabolism
Lysophospholipids - agonists
Lysophospholipids - pharmacology
Neoplasms - drug therapy
Phosphotransferases (Alcohol Group Acceptor) - antagonists & inhibitors
Practolol - metabolism
Sphingosine - agonists
Sphingosine - analogs & derivatives
Sphingosine - metabolism
Sphingosine - pharmacology
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Sphingosine kinase (SphK) is an oncogenic lipid kinase that regulates the sphingolipid metabolic pathway that has been shown to play a role in numerous hyperproliferative/inflammatory diseases. The SphK isoforms (SphK1 and SphK2) catalyze the conversion of the proapoptotic substrate d-erythrosphingosine to the promitogenic/migratory product sphingosine 1-phosphate (S1P). Accumulation of S1P has been linked to the development/progression of cancer and various other diseases including, but not limited to, asthma, inflammatory bowel disease, rheumatoid arthritis, and diabetic nephropathy. SphK therefore represents a potential new target for developing novel therapeutics for cancer and other diseases. This finding has stimulated the development and evaluation of numerous SphK inhibitors over the past decade or so. In this review, we highlight the recent advancement in the field of SphK inhibitors including SphK1 and SphK2 specific inhibitors. Both sphingolipid based and nolipidic small molecule inhibitors and their importance in treatment of cancer and other diseases are discussed.
ISSN:1520-4804
DOI:10.1021/jm4011687