Development of a sphingosine kinase 1 specific small-molecule inhibitor

Jeremy Hengst, Xujun Wang, Ugir H. Sk, Arun Sharma, Shantu Amin, Jong Yun

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The sphingolipid metabolic pathway represents a potential source of new therapeutic targets for numerous hyperproliferative/inflammatory diseases. Targets such as the sphingosine kinases (SphKs) have been extensively studied and numerous strategies have been employed to develop inhibitors against these enzymes. Herein, we report on the optimization of our novel small-molecule inhibitor SKI-I (N′-[(2-hydroxy-1-naphthyl)methylene]-3-(2-naphthyl)-1H- pyrazole-5-carbohydrazide) and the identification of a SphK1-specific analog, SKI-178, that is active in vitro and in vivo. This SphK1 specific small-molecule, non-lipid like, inhibitor will be of use to elucidate the roles of SphK1 and SphK2 in the development/progression of hyperproliferative and/or inflammatory diseases.

Original languageEnglish (US)
Pages (from-to)7498-7502
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume20
Issue number24
DOIs
StatePublished - Dec 15 2010

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Sphingolipids
Molecules
Enzyme Inhibitors
Metabolic Networks and Pathways
Enzymes
sphingosine kinase
Therapeutics
pyrazole
In Vitro Techniques
N'-((1E)-1-(3,4-dimethoxyphenyl)ethylidene)-3-(4-methoxyphenyl)-1H-pyrazole-5-carbohydrazide
carbohydrazide

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

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Development of a sphingosine kinase 1 specific small-molecule inhibitor. / Hengst, Jeremy; Wang, Xujun; Sk, Ugir H.; Sharma, Arun; Amin, Shantu; Yun, Jong.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 20, No. 24, 15.12.2010, p. 7498-7502.

Research output: Contribution to journalArticle

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