FTI 277 HCl is the methyl ester of FTI 277, which is a potent and selective farnesyltransferase (FTase) inhibitor with IC50 of 500 pM, about 100-fold selectivity over the closely related GGTase I. FTI 277 HCl inhibits cell growth and induces apoptosis. FTI 277 HCl is effective in clearing HDV viremia.
FTI-277 inhibits Ras processing with an IC50 of 100 nM, but not the geranylgeranylated Rap1A processing in whole cells. FTI-277 induces accumulation of cytoplasmic non-farnesylated H-Ras, accumulates inactive Ras/Raf complexes in the cytoplasm, and blocks constitutive MAPK activation in H-RasF cells. [1] FTI-277 causes increased apoptosis after irradiation and increases radiosensitivity in H-ras-transformed rat embryo cells. [2] FTI-277 also inhibits cell growth and induces apoptosis in drug-resistant myeloma tumor cells. [3] In SH-SY5Y cells, FTI-277 diminishes the toxic effects of methamphetamine on induction in cell degeneration, activation in c-Jun-N-terminal kinase cascades, and Ras activation. [4]
In mice coinfected with hepatitis B virus (HBV) and HDV, FTI-277 (50 mg/kg/d i.p.) effectively clears HDV viremia. [5]
[1] Lerner EC, et al. J Biol Chem. 1995, 270(45), 26802-26806. [2] Bernhard EJ, et al. Cancer Res. 1996, 56(8), 1727-1730. [3] Bolick SC, et al. Leukemia. 2003, 17(2), 451-457