Ras famesyltransferase inhibitor

Hinterding K, Hagenbuch P, Retey J, Waldmann H (1998) Synthesis and In Vitro Evaluation of the Ras Famesyltransferase Inhibitor Pepticinnamin E. Angew Chem Int Ed 37 1236... 

Waldmann H, Thutewohl M (2000) Ras-Famesyltransferase-Inhibitors as Promising Anti-Tumor Drugs. 211 117-130 WangG-X,see ChowH-F (2001)217 1-50 Weil T, see Wiesler U-M (2001) 212 1-40... 

Several methods are being studied to enhance the stabiUty of peptide mimics and improve their stereochemical similarity to the endogenous peptides. For example, the tetrapeptide Cys—Val—Phe—Met, a potent inhibitor of Ras famesyltransferase, is proposed to exist in a turned conformation, which mimics the endogenous peptide during enzyme binding. This conformation is successhiUy mimicked by 3-amino-l-carboxymethyl-5-phenyl-benzodiazepin-2-onederivatives (198) (142). 

Work, L.M., McPhaden, A.R., Pyne, N.J., Pyne, S., Wadsworth, R.M., and Wainwright, C.L. (2001). Short-term local dehvery of an inhibitor of Ras famesyltransferase prevents neoin-tima formation in vivo after porcine coronary balloon angioplasty. Circulation 104 1538-1543. 

Gibbs J. B., Oliflf A., Kohl N. E. (1994) Famesyltransferase inhibitors Ras research yields a potential cancer therapeutic. Cell 77 175. 

Famesyltransferase inhibitors as potential anticancer drugs In 1989, it was discovered that famesylation of a cysteine residue near the ras gene protein s C-terminus is required for its biological activity. Interfering with Ras function by blocking the enzyme responsible for its... 

Clark MK, Scott SA, Wojtkowiak J, Chirco R, Mathieu P, Reiners JJ Jr, Mattingly RR, Botch RF, Gibbs RA (2007) Synthesis, biochemical, and cellular evaluation of famesyl monophosphate prodrags as famesyltransferase inhibitors. J Med Chem 50 3274—3282... 

Famesyltransferase inhibitors (FTI) have antitumor activity by inhibiting the famesylation of several intracellular proteins involved in cell proliferation (ras, MEK, ART). 

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