Sphingosine kinase inhibitors: A patent review

  • Authors:
    • Mengda Cao
    • Chunmei Ji
    • Yanjun Zhou
    • Wen Huang
    • Weiwei Ni
    • Xunliang Tong
    • Ji-Fu Wei
  • View Affiliations

  • Published online on: February 20, 2018     https://doi.org/10.3892/ijmm.2018.3505
  • Pages: 2450-2460
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Abstract

Sphingosine kinases (SphKs) catalyze the conversion of the sphingosine to the promitogenic/migratory product, sphingosine-1-phosphate (S1P). SphK/S1P pathway has been linked to the progression of cancer and various other diseases including allergic inflammatory disease, cardiovascular diseases, rejection after transplantation, the central nervous system, and virus infections. Therefore, SphKs represent potential new targets for developing novel therapeutics for these diseases. The history and development of SphK inhibitors are discussed, summarizing SphK inhibitors by their structures, and describing some applications of SphK inhibitors. We concluded: i) initial SphK inhibitors based on sphingosine have low specificity with several important off-targets. Identification the off-targets that would work synergistically with SphKs, and developing compounds that target the unique C4 domain of SphKs should be the focus of future studies. ii) The modifications of SphK inhibitors, which are devoted to increasing the selectivity to one of the two isoforms, now focus on the alkyl length, the spacer between the head and linker rings, and the insertion and the position of lipidic group in tail region. iii) SphK/S1P signaling pathway holds therapeutic values for many diseases. To find the exact function of each isoform of SphKs increasing the number of SphK inhibitor clinical trials is necessary.
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May-2018
Volume 41 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Cao M, Ji C, Zhou Y, Huang W, Ni W, Tong X and Wei J: Sphingosine kinase inhibitors: A patent review. Int J Mol Med 41: 2450-2460, 2018.
APA
Cao, M., Ji, C., Zhou, Y., Huang, W., Ni, W., Tong, X., & Wei, J. (2018). Sphingosine kinase inhibitors: A patent review. International Journal of Molecular Medicine, 41, 2450-2460. https://doi.org/10.3892/ijmm.2018.3505
MLA
Cao, M., Ji, C., Zhou, Y., Huang, W., Ni, W., Tong, X., Wei, J."Sphingosine kinase inhibitors: A patent review". International Journal of Molecular Medicine 41.5 (2018): 2450-2460.
Chicago
Cao, M., Ji, C., Zhou, Y., Huang, W., Ni, W., Tong, X., Wei, J."Sphingosine kinase inhibitors: A patent review". International Journal of Molecular Medicine 41, no. 5 (2018): 2450-2460. https://doi.org/10.3892/ijmm.2018.3505