FTI-277 hydrochloride (FTI 277 HCl) is an effective and specific farnesyltransferase (FTase) inhibitor (IC50: 500 pM); this selectivity is about 100-fold than the closely related GGTase I.

FTase:500 pM

In mouse models infected with Hepatitis B Virus (HBV) and Hepatitis D Virus (HDV), FTI-277 administered intraperitoneally at a dosage of 50 mg/kg/day effectively clears Hepatitis D viremia.

In drug-resistant myeloma cells, FTI-277 inhibits cell growth and induces apoptosis. It mitigates the toxicity induced by methamphetamine in SH-SY5Y cells through effects on cell degeneration, activation, the c-Jun N-terminal kinase cascade, and the Ras activation process. FTI-277 inhibits Ras processing (IC50: 100 nM) without affecting the overall cellular prenylation of Rap1A. Additionally, FTI-277 increases post-irradiation apoptosis and enhances the radiation sensitivity of H-ras transformed rat embryo cells.

FTase and GGTase I Activity Assay: FTase and GGTase I activities from 60,000×g supernatants of human Burkitt lymphoma (Daudi) cells are assayed. Inhibition studies are performed by determining the ability of Ras CAAX peptidomimetics to inhibit the transfer of [3H]farnesyl and [3H]geranylgeranyl from [3H]farnesylpyrophosphate and [3H]geranylgeranylpyrophosphate to H-Ras-CVLS and H-Ras-CVLL, respectively.

Cells are seeded at 8000–14 000 cells/well in 96-well plates. To establish a dose–response to FTI-277, cells are incubated for 96 h in two-fold serial dilutions ranging from 3.75 times 10-7 M to 1 times 10-5 M. Following continuous drug exposure, 50 μL MTT dye is added. The insoluble formazan complex is solubilized with DMSO and absorbance measured at 540 nm. IC50s and 95% confidence intervals are calculated by regression analysis of the linear portion of the dose–response curve. (Only for Reference)