INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE

摘要

The present invention comprises analogs of the CAAX motif of the protein Ras that is modified by farnesylation vivo. These CAAX analogs inhibit the farnesylation of Ras. Furthermore, these CAAX analogs differ from those previously described as inhibitors of Ras famesyl transferase in that they do not bave a thiol moiety. The lack of the thiol offers unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol-dependent chemical reactions, such as rapid autoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production.