Over the last two decades, we have seen intensive drug discovery efforts aimed at developing cancer therapeutics that specifically target the underlying defects in cellular growth regulation. By virtue of their specificity, these gene-targeted therapeutics are anticipated to be more effective and less toxic than the currently used chemotherapeutic agents. Among the oncogenes associated with human cancers, the ras oncogenes stand out as particularly attractive targets for creation of cancer therapeutics. These genes have been implicated in upto 30% of human cancers and are most commonly found in pancreatic cancer, colon cancer, and adenocarcinoma of the lung. The ras proto-oncogene encodes a 21-kd GTP-binding protein Ras, which is critical in cellular signal transduction associated with cell proliferation. To function in this signal transduction process, Ras must localize to the plasma membrane. A key step in this translocation is the post translational farnesylation of the cysteine residue near the carboxyl-terminal of Ras that is effected by the enzyme, farnesyl protein transferase. Inhibition of Ras farnesylation is therefore a promising approach for developing mechanism-based anticancer drugs.
Keywords: farnesyl transferase inhibitors, Anticancer therapeutic, 21-kd GTP-binding protein, Pyridine-N-Oxides, Bromo Substitutes, Dihalogenated Tricyclic, Trihalo Tricyclic ftis, 3,8,10-Trihalo Tricyclic FTI, FTase
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