Pachastrissamine (jaspine B) and its stereoisomers inhibit sphingosine kinases and atypical protein kinase C

Yuji Yoshimitsu, Shinya Oishi, Jun Miyagaki, Shinsuke Inuki, Hiroaki Ohno, Nobutaka Fujii

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Sphingosine kinases (SphKs) are oncogenic enzymes that regulate the critical balance between ceramide and sphingosine-1-phosphate. Much effort has been dedicated to develop inhibitors against these enzymes. Naturally occurring pachastrissamine (jaspine B) and all its stereoisomers were prepared and evaluated for their inhibitory effects against SphKs. All eight stereoisomers exhibited moderate to potent inhibitory activity against SphK1 and SphK2. Inhibitory effects were profiled against protein kinase C (PKC) isoforms by in vitro experiments. Atypical PKCs (PKCζ and PKCι) were inhibited by several pachastrissamine stereoisomers. The improved activity over N,N-dimethylsphingosine suggests that the cyclic scaffold in pachastrissamines facilitates potential favorable interactions with SphKs and PKCs.

Original languageEnglish
Pages (from-to)5402-5408
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume19
Issue number18
DOIs
Publication statusPublished - 2011 Sep 15
Externally publishedYes

Fingerprint

Stereoisomerism
Protein Kinase C
Ceramides
Enzyme Inhibitors
Enzymes
Scaffolds
Protein Isoforms
sphingosine kinase
pachastrissamine
PKC-3 protein
Experiments

Keywords

  • Jaspine B
  • Pachastrissamine
  • Protein kinase C
  • Sphingolipid
  • Sphingosine kinase

ASJC Scopus subject areas

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

Cite this

Pachastrissamine (jaspine B) and its stereoisomers inhibit sphingosine kinases and atypical protein kinase C. / Yoshimitsu, Yuji; Oishi, Shinya; Miyagaki, Jun; Inuki, Shinsuke; Ohno, Hiroaki; Fujii, Nobutaka.

In: Bioorganic and Medicinal Chemistry, Vol. 19, No. 18, 15.09.2011, p. 5402-5408.

Research output: Contribution to journalArticle

Yoshimitsu, Yuji ; Oishi, Shinya ; Miyagaki, Jun ; Inuki, Shinsuke ; Ohno, Hiroaki ; Fujii, Nobutaka. / Pachastrissamine (jaspine B) and its stereoisomers inhibit sphingosine kinases and atypical protein kinase C. In: Bioorganic and Medicinal Chemistry. 2011 ; Vol. 19, No. 18. pp. 5402-5408.
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