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Mutant ras oncogenes are associated with various human tumors, being found in approximately 25% of all human cancers. Since its identification, the enzyme Ras protein farnesyltransferase (PFTase), which catalyzes the initial step of Ras-processing, has been viewed as a most promising target for cancer therapy. Consequently, a number of synthetic and natural small molecules have been searched and developed according to this concept during the 1990s. Among these, microbial metabolites have provided diverse structural classes of compounds which exhibit PFTase inhibitory activity. This article reviews our work on PFTase inhibitors originating from microbial metabolites, and the results of similar works carried out by several other research groups.

Search for Protein Farnesyltransferase Inhibitors of Microbial Origin: Our Strategy and Results as well as the Results Obtained by Other Groups