FTI-277

FTI-277 is a potent, cell-permeable peptidomimetic small molecule that acts as a farnesyltransferase inhibitor (FTI). It is the methyl ester prodrug of FTI-276, designed to enhance cellular uptake and potency. FTI-277 functions by mimicking the C-terminal CAAX motif (specifically the CVIM sequence) of Ras proteins, thereby competitively inhibiting the enzyme protein farnesyltransferase (FTase). This inhibition prevents the post-translational farnesylation of Ras isoforms, such as H-Ras and K-Ras, which is a critical step for their membrane localization and activation of downstream oncogenic signaling pathways, including the Raf-1/MEK/ERK and PI3K/Akt pathways. In preclinical research, FTI-277 has been shown to induce G0/G1 cell cycle arrest and apoptosis in various cancer cell lines, including liver, bladder, prostate, and breast cancers, often by modulating the expression of Bcl-2 family proteins and cyclin-dependent kinase inhibitors like p21WAF1 and p27KIP1.

Other names

Farnesyltransferase Inhibitor 277