FTI-277 (TFA)

FTI-277 TFA is a farnesyltransferase (FTase) inhibitor. FTI-277 TFA inhibits Ras farnesylation, blocks the phosphorylation of downstream ERK1/2 and mTOR, and reduces membrane-bound active N-ras protein. FTI-277 TFA activates caspase 3, upregulates Bim expression, induces cell apoptosis, suppresses regulatory T cell expansion, enhances macrophage phagocytosis, and improves bacterial clearance. FTI-277 TFA activates the PI3K/Akt signaling pathway, inhibits osteoblast differentiation, and reduces the proliferation ability of neuroblastoma cells. FTI-277 TFA can be used in research related to head and neck squamous cell carcinoma, neuroblastoma, sepsis, and vascular calcification^[1][2][3][4]. In Vitro:FTI-277 (1-40 μM; 24-72 h) TFA decreases the viability of HEp-2 head and neck squamous cell carcinoma cells in a concentration-dependent manner, with a 58.5% reduction in viability at the highest tested concentration (40 μM) after 72 h of treatment^[1].
FTI-277 (0.5-10 μM; 24-72 h) TFA decreases the viability of HSC-3 head and neck squamous cell carcinoma cells in a concentration-dependent manner, with a 77.0% reduction in viability at the highest tested concentration (10 μM) after 72 h of treatment, and exhibits greater potency against HSC-3 cells than HEp-2 cells^[1].
FTI-277 (40 μM; 36 h) TFA significantly increases caspase-3 activity in HEp-2 head and neck squamous cell carcinoma cells[1].
FTI-277 (5 μM; 36 h) TFA significantly increases caspase-3 activity in HSC-3 head and neck squamous cell carcinoma cells, demonstrating greater potency than against HEp-2 cells^[1].
FTI-277 (40 μM; 36 h) TFA significantly increases the percentage of annexin V-positive HEp-2 head and neck squamous cell carcinoma cells, indicating induction of apoptosis^[1].
FTI-277 (5 μM; 36 h) TFA significantly increases the percentage of annexin V-positive HSC-3 head and neck squamous cell carcinoma cells, indicating induction of apoptosis with greater potency than against HEp-2 cells^[1].
FTI-277 (40 μM; 48 h) TFA suppresses Ras membrane localization, reduces phosphorylation of ERK1/2 and mTOR, and increases Bim protein expression in HEp-2 head and neck squamous cell carcinoma cells^[1].
FTI-277 (5 μM; 48 h) TFA suppresses Ras membrane localization, reduces phosphorylation of ERK1/2 and mTOR, and increases Bim protein expression in HSC-3 head and neck squamous cell carcinoma cells, demonstrating greater potency than against HEp-2 cells^[1].
FTI-277 (5 μM; 72 h) TFA significantly decreases the viability of NW7 v-H-Ras-transfected NIH3T3 cells but has no significant effect on NV20 empty vector-transfected NIH3T3 cells, indicating selective activity against Ras-overexpressing cells^[1].
FTI-277 (1-20 μM; 8-10 days) TFA inhibits osteogenic differentiation and βGP-induced mineralization in primary bovine vascular smooth muscle cells, with significant effects observed at concentrations ≥10 μM, and even when added up to 6 days post-βGP initiation^[3].
FTI-277 (10 μM; 77 h) TFA enhances Akt phosphorylation in primary bovine vascular smooth muscle cells when followed by serum starvation and short-term serum stimulation^[3].
FTI-277 (10-20 μM; 9-10 days) TFA maintains Akt phosphorylation during βGP-induced mineralization in primary bovine vascular smooth muscle cells, and this Akt activation is required for FTI-277's inhibitory effect on mineralization^[3].
FTI-277 (10 μM) TFA inhibits phosphate-induced apoptosis in human coronary artery vascular smooth muscle cells, and this effect depends on Akt activation^[3].
FTI-277 (10 μM; 96 h) TFA reduces farnesylated N-Ras protein levels by approximately 50% in IMR-5 neuroblastoma cells^[4].
FTI-277 (10 μM; 96 h) TFA reduces basal MAP-kinase activity by ~47% and blunts BDNF-induced MAP-kinase activation to 35% of control levels in IMR-5 neuroblastoma cells^[4].
FTI-277 (10 μM; 96 h) TFA reduces basal N-myc expression to 70% of controls and blunts BDNF-induced N-myc expression to 53% of control-stimulated levels in IMR-5 neuroblastoma cells^[4].
FTI-277 (10 μM; 96 h) TFA significantly reduces cell proliferation across complete, serum-free, and BDNF-supplemented media, and abolishes BDNF-induced proliferation in IMR-5 neuroblastoma cells^[4]. In Vivo:FTI-277 (25 mg/kg; i.p.; single dose) TFA administered 2 hours post-CLP reduces septic mouse mortality to a 67% survival rate, while improving bacterial clearance, reversing immune dysfunction, and suppressing sepsis-induced protein farnesylation^[2].