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

Farnesyl-protein transferase (FPTase) catalyses the specific transfer of fa rnesyl 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 ra s, thereby establishing FPTase as a viable therapeutic target. Our continue d efforts to discover inhibitors of FPTase has led to the discovery of a tr iterpenoidal inhibitor, clavaric acid (1). This compound inhibits rHFPTase with an IC50 value of 1.3 mu M. Structure elucidation, structure modificati ons, and biological activity of clavaric acid are herein described.