Farnesyltransferase (farnesyltransferase, FTase) is composed of the α subunit encoded by the FNTA gene and the β subunit encoded by the FNTB gene. FTase recognizes the C-terminal CAAX motif of the RAS protein. This step is essential for the cell membrane localization and biological activity of the RAS protein. Farnesylated RAS protein is equivalent to a signal transduction switch. RAS protein plays an important role in the formation and development of tumors. RAS protein controls cell signaling pathways and participates in cell growth, migration, adhesion, cytoskeleton integrity, survival and differentiation, and other functions. Tipifarnib (IND 58359) inhibits farnesyltransferase (FTase) with an IC50 of 0.86 nM. It has potential antineoplastic activity.

Tipifarnib (IND 58359) is a potent FTase Inhibitor with antineoplastic activity.

In some in vitro studies, Tipifarnib inhibits the growth of H-Ras-transformed NIH 3T3 cells with an impressive IC50 value of 1.7 nM. Besides, it inhibits isolated human farnesyltransferase for a lamin B peptide and for the K-RasB peptide with IC50 of 0.86 nM and 7.9 nM, respectively. Moreover, Tipifarnib shows inhibition of cell growth or angiogenesis and induction of apoptosis in aggressive prostate cancer (PCa). In addition, Tipifarnib (1 μM) significantly inhibits the protein concentration of Alix, nSMase2, and Rab27a in C4-2B cells. Also, it significantly inhibits the activation of p-ERK in C4-2B and PC-3 cells but not in the normal RWPE-1 cells. Importantly, Tipifarnib (0-250 nM) causes a dose-dependent decrease in Alix, nSMase2, and Rab27a in both C4-2B and PC-3 cells, but not in the RWPE-1 cells.

In vivo studies, combined therapy with ICI 47699 and Tipifarnib (50 mg/kg, p.o.) produces greater tumor growth inhibition when compared with either drug alone. Firstly, E2 deprivation and Tipifarnib in combination result in greater growth inhibition than either E2 deprivation or Tipifarnib alone. Secondly, the combination of ICI 47699 and Tipifarnib results in significantly lower Ki-67 compared with either ICI 47699 or Tipifarnib alone. Tipifarnib alone also reduces the CTI compared with the control.


[1] Devendra S Puntambekar, et al. J Enzyme Inhib Med Chem. 2007 Apr;22(2):127-40.

[2] Lesley-Ann Martin, et al. Mol Cancer Ther. 2007 Sep;6(9):2458-67.