Clavaric acid: a triterpenoid inhibitor of farnesyl-protein transferase from Clavariadelphus truncatus

J Nat Prod. 1998 Dec;61(12):1568-70. doi: 10.1021/np980200c.

Abstract

Farnesyl-protein transferase (FPTase) catalyses the specific transfer of farnesyl to Ras-peptides that is essential for oncogenic activity in oncogene-mediated tumors. Specific inhibition of FPTase activity has been shown to reduce tumor development in nude mice challenged with oncogenic forms of ras, thereby establishing FPTase as a viable therapeutic target. Our continued efforts to discover inhibitors of FPTase has led to the discovery of a triterpenoidal inhibitor, clavaric acid (1). This compound inhibits rHFPTase with an IC50 value of 1.3 microM. Structure elucidation, structure modifications, and biological activity of clavaric acid are herein described.

MeSH terms

  • Alkyl and Aryl Transferases / antagonists & inhibitors*
  • Animals
  • Basidiomycota / chemistry*
  • Enzyme Inhibitors / isolation & purification*
  • Enzyme Inhibitors / pharmacology
  • Fermentation
  • Hydrolysis
  • Lanosterol / analogs & derivatives*
  • Lanosterol / isolation & purification
  • Lanosterol / pharmacology
  • Methylation
  • Mice
  • Spectrophotometry, Infrared

Substances

  • Enzyme Inhibitors
  • clavaric acid
  • Lanosterol
  • Alkyl and Aryl Transferases
  • p21(ras) farnesyl-protein transferase