Abstract
There is considerable evidence that sphingosine kinases play a key role in cancer progression, which might involve positive selection of cancer cells that have been provided with a survival and growth advantage as a consequence of overexpression of the enzyme. Therefore, inhibitors of sphingosine kinase represent a novel class of compounds that have potential as anticancer agents. Poor inhibitor potency is a major issue that has precluded successful translation of these compounds into the clinic. However, recent discoveries have shown that sphingosine kinase 1 is an allosteric enzyme and that some inhibitors offer improved effectiveness by inducing proteasomal degradation of the enzyme or having nanomolar potency. Herein, we provide a perspective about these recent developments and highlight the importance of translating basic pharmacologic and biochemical findings on sphingosine kinase into new drug discovery programs for treatment of cancer.
Original language | English |
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Pages (from-to) | 6576-6582 |
Number of pages | 7 |
Journal | Cancer Research |
Volume | 71 |
Issue number | 21 |
Early online date | 22 Sept 2011 |
DOIs | |
Publication status | Published - 2011 |
Keywords
- sphingosine kinase inhibitors
- cancer
- hercules
- golden sword