Inhibitor farnesyltransferase

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

Waldmann H, Thutewohl M (2000) Ras-Farnesyltransferase-Inhibitors as Promising Anti-Tiimor Drugs. 211 117-130... 

Ras is strictly localized to the inner side of the plasma membrane. A lipid anchor covalently attached to the C-terminus of Ras penetrates into the lipid bilayer. This membrane anchorage is essential for the biological activity of Ras. Hence, the inhibition of anchor attachment has become an attractive pharmacological target [ 13]. See Waldmann H, Thutewohl M,Ras-Farnesyltransferase-inhibitors as promising anti-tumor drugs, this volume. 

Ras-Farnesyltransferase-Inhibitors as Promising Anti-Tumor Drugs... 

Toxicity and effectivity studies have often been performed in rodent fibroblast cells containing oncogenic H-Ras. However, prenylation of K-Ras B and N-Ras are not as effectively blocked by the farnesyltransferase inhibitors as H-Ras [48] (see below). Thus normal cells may be less sensitive to these drugs because they express K-Ras 4B and N-Ras. In this context it should be noted that H-Ras mutations are relatively uncommon in human tumors [49]. Rather, the K-Ras gene is the most frequently mutated in solid human cancers, whereas N-Ras is prevalent in leukemias. Thus the preclinical evaluation of the farnesylation inhibitors has yet to be critically re-evaluated for trials in humans. 

Aminopyrrolidinone farnesyltransferase inhibitors design of macrocyclic compounds with improved pharmacokinetics and excellent cell potency. Journal of Medicinal Chemistry, 45, 2388-2409. 

Farnesyltransferase inhibitor, IC5Q 25 pM from structure-based virtual screening... 

Cox AD, Der CJ. Farnesyltransferase inhibitors promises and reahties. Curr Opin Pharmacol 2002 2 388-93. 

Patnaik A, Rowinsky EK (2001) Early clinical experience with farnesyl protein transferase inhibitors. In Sebti SM, Hamilton AD (eds) Farnesyltransferase inhibitors in cancer therapy. Humana, Totowa, NJ, pp 233-249... 

Farnesyltransferase Inhibitors in Cancer, edited by Said M. Sebti and Andrew D. Hamilton, 2001... 

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