Sphingosine kinase inhibitors and cancer: seeking the golden sword of Hercules

Susan Pyne, Robert Bittman, Nigel Pyne

Research output: Contribution to journalArticle

67 Citations (Scopus)

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.
LanguageEnglish
Pages6576-6582
Number of pages7
JournalCancer Research
Volume71
Issue number21
Early online date22 Sep 2011
DOIs
Publication statusPublished - 2011

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Neoplasms
Enzyme Inhibitors
Enzymes
Drug Discovery
Antineoplastic Agents
sphingosine kinase
Growth

Keywords

  • sphingosine kinase inhibitors
  • cancer
  • hercules
  • golden sword

Cite this

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Sphingosine kinase inhibitors and cancer : seeking the golden sword of Hercules. / Pyne, Susan; Bittman, Robert; Pyne, Nigel.

In: Cancer Research, Vol. 71, No. 21, 2011, p. 6576-6582.

Research output: Contribution to journalArticle

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