Farnesyl Thiosalicylic Acid Amide, association of Ras protein to the inner surface of the plasma membrane is required for Ras signaling activity. Farnesyl thiosalicylic acid (FTS) inhibits Ras-mediated signaling by dislodging Ras from the cell membrane thereby rendering it susceptible to proteolytic degradation. FTS amide is an FTS derivative with an amide added to the carboxyl group. FTS amide inhibits the growth of U87 and Panc-1 tumor cells with IC50values of 10 and 20 μM, respectively, a relatively higher potency compared to that of FTS (IC50s = 50 and 35 μM, respectively). Treatment of nude mice bearing either Panc-1 or U87 glioblastoma tumors with 100 mg/kg FTS-amide twice daily for four days inhibits tumor growth by at least 50% of controls.
1 Haklai, R., Weisz, M.G., Elad, G., et al. Dislodgment and accelerated degradation of ras. Biochemistry 37 1306-1314 (1998). 2 Goldberg, L., Haklai, R., Bauer, V., et al. New derivatives of farnesylthiosalicylic acid (salirasib) for cancer treatment: Farnesylthiosalicylamide inhibits tumor growth in nude mice models. J Med Chem 52 197-205 (2009).
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