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

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.

Journal

• Bioorganic & medicinal chemistry

  Bioorganic & medicinal chemistry 19 (18), 5402-5408, 2011-09-15

  Elsevier BV

Keywords

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

Details

• CRID: 1050845760651091840
• NII Article ID: 120003386631
• NII Book ID: AA10938083
• ISSN: 09680896
• HANDLE: 2433/147238
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • CiNii Articles