FTI 276 TFA is a protein farnesyl transferase (PFT) inhibitor with an IC50 value of 1nM [1]. FTI 276 TFA can block Ras oncogenic signaling and prevent constitutive activation of the MAPK cascade [2]. FTI 276 TFA has been widely used to inhibit tumor growth in the primary mouse lung tumor model [3].
In vitro, FTI 276 TFA treatment (50μM) for 24 hours significantly reduced the extracellular MMP-1 level in 143B cells and inhibited the invasion of 143B cells[4].
In vivo, FTI 276 TFA treatment via daily intraperitoneal injection at a dose of 70mg/kg for 80 days significantly inhibited the growth of A549 xenograft tumors (express K-Ras mutations) in mice[5]. Intravenous infusion of 307μg/kg/day dose of FTI 276 TFA for 3 weeks significantly reduced myocardial fibrosis and improved cardiac remodeling in spontaneously hypertensive rats [6]. Continuous intraperitoneal injection of 50mg/kg/day dose of FTI 276 TFA for 36 consecutive days significantly inhibited tumor growth in the Calu-1 xenograft mouse model[7].
References:
[1] Chakrabarti D, Da Silva T, Barger J, et al. Protein Farnesyltransferase and Protein Prenylation inPlasmodium falciparum[J]. Journal of Biological Chemistry, 2002, 277(44): 42066-42073.
[2] Lerner E C, Qian Y, Blaskovich M A, et al. Ras CAAX peptidomimetic FTI-277 selectively blocks oncogenic Ras signaling by inducing cytoplasmic accumulation of inactive Ras-Raf complexes[J]. Journal of Biological Chemistry, 1995, 270(45): 26802-26806.
[3] Lantry L E, Zhang Z, Crist K A, et al. Chemopreventive efficacy of promising farnesyltransferase inhibitors[J]. Experimental lung research, 2000, 26(8): 773-790.
[4] Garamszegi N, Garamszegi S P, Scully S P. Matrix metalloproteinase‐1 contribution to sarcoma cell invasion[J]. Journal of cellular and molecular medicine, 2012, 16(6): 1331-1341.
[5] Sun J, Qian Y, Hamilton A D, et al. Both farnesyltransferase and geranylgeranyltransferase I inhibitors are required for inhibition of oncogenic K-Ras prenylation but each alone is sufficient to suppress human tumor growth in nude mouse xenografts[J]. Oncogene, 1998, 16(11): 1467-1473.
[6] Li X, Han J, Li L, et al. Effect of farnesyltransferase inhibition on cardiac remodeling in spontaneously hypertensive rats[J]. International journal of cardiology, 2013, 168(4): 3340-3347.
[7] Sun J, Qian Y, Hamilton A D, et al. Ras CAAX peptidomimetic FTI 276 selectively blocks tumor growth in nude mice of a human lung carcinoma with K-Ras mutation and p53 deletion[J]. Cancer research, 1995, 55(19): 4243-4247.