Association of Ras protein with the inner surface of the plasma membrane is required for Ras signaling activity. Farnesyl thiosalicylic acid (FTS) is an inhibitor of Ras-
mediated signaling that functions by dislodging Ras from the cell membrane thereby rendering it susceptible to proteolytic degradation.
1 FTS inhibits the growth of human Ha-
ras-
transformed Rat1 fibroblasts with an IC
50 value of 7.5 μM.
2 It does not inhibit Ras farnesylation
in vitro and although FTS does inhibit prenylated protein methyltransferase (PPMTase) in cell-
free systems with a K
i value of 2.6 μM, it is relatively ineffective at inhibiting methylation in whole cells.
3 Treatment of chow-
fed ApoE-
deficient mice with 5 mg/kg FTS three times per week for six weeks reduces early atherosclerotic lesion development by 52% compared to controls.
4