GGTI-286, a potent and cell-permeable GGTase I inhibitor, is 25-fold more potent ( IC 50 =2 μM) than the corresponding methyl ester of FTI-276 ( HY-15873A ). GGTI-286 selectively inhibits geranylgeranylation of Rap1A over farnesylation of H-Ras in NIH3T3 cells ( IC 50 s =2 and >30 μM, respectively). GGTI-286 also potently inhibits oncogenic K-Ras4B stimulation with an IC 50 of 1 μM.
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