244013-66-9Relevant academic research and scientific papers
Design, synthesis and early structure-activity relationship of farnesyltransferase inhibitors which mimic both the peptidic and the prenylic substrate
Schlitzer, Martin,Boehm, Markus,Sattler, Isabel,Dahse, Hans-Martin
, p. 1991 - 2006 (2007/10/03)
Inhibition of the farnesylation of ras proteins has been identified as a promising target in tumor therapy. Only a few farnesyltransferase inhibitors are bisubstrate analogues displaying features of both substrates, the farnesylpyrophosphate and the C-terminal CAAX-tetrapeptide sequence of the ras protein. These known bisubstrate analogues consist of an AAX-tripeptide and a farnesyl residue connected through various linkers. We have developed a class of novel compounds that mimic a bisubstrate inhibitor structure and that differ from the known ones by lacking peptidic or farnesylic substructures. Long chain fatty acids and aryl-substituted carboxylic acids were used as farnesyl surrogates. These structures were linked to isoleucine amide, benzoic acid amide, N-substituted aminobenzenesulfonamides and N(α)-aryl-substituted methionine derivatives, respectively, which function as AA- or AAX-mimetics. Copyright (C) 2000 Elsevier Science Ltd.
Different amino acid replacements in CAAX-tetrapeptide based peptidomimetic farnesyltransferase inhibitors
Schlitzer, Martin,Sattler, Isabel,Dahse, Hans-Martin
, p. 124 - 132 (2007/10/03)
In a series of CAAX-tetrapeptide based farnesyltransferase inhibitors it has been shown that the central AA-dipeptide can be replaced by tranexamic acid, 4-aminobenzenesulfonic acid, and 3-amino-N-(2,3- dimethylphenyl)benzenesulfonamide, respectively, yielding inhibitors active in the low micromolar range. Lipophilic derivatives of these compounds showed moderate antiproliferative activity against different tumor cell lines. A promising class of peptidomimetic farnesyltransferase inhibitors was discovered through the replacement of the terminal AAX motif of the CAAX- tetrapeptide by 2-acylamino-5-aminobenzophenones.
Design, synthesis, and evaluation of novel modular bisubstrate analogue inhibitors of farnesyltransferase
Schlitzer, Martin,Sattler, Isabel
, p. 2032 - 2034 (2007/10/03)
Promising potential chemotherapeutics for the treatment of cancer can be developed from farnesyltransferase inhibitors. A novel class of modular bisubstrate farnesyltransferase inhibitors is presented that can be synthesized in a straightforward manner. A
