The present invention comprises analogs of the CAAX motif of the protein Ras that is modified by farnesylation in vivo. These CAAX analogs inhibit farnesyl-protein transferase. Furthermore, these CAAX analogues differ from those previously described as inhibitors of farnesyl-protein transferase in that they do not have 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 antoxidation 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.
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(2008/06/13)
Inhibitors of farnesyl-protein transferase
The present invention comprises analogs of the CA1 A2 X motif of the protein Ras that is modified by farnesylation in vivo. These CA1 A2 X analogs inhibit the farnesylation of Ras. Furthermore, these CA1/s