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Farnesyl-derived inhibitors of ras farnesyl transferase
M S Kang1, D M Stemerick, J H Zwolshen
1Hoechst Marion Roussel, Inc., Cincinnati, Ohio 45215, USA.
Abstract:
The synthesis and evaluation of farnesyl-derived inhibitors of ras farnesyl transferase are presented. Evaluation of inhibitors of farnesyl transferase and comparison with the previously described inhibitor was accomplished using purified enzyme and Amersham's Farnesyl:Transferase enzyme assay kit. These results show an order of magnitude increase in inhibitory activity for beta-ketophosphonic acid over beta-hydroxyphosphonic acid. Incorporation of fluorines in alpha-position, led to an increase in inhibitory activity over the nonfluorinated analogues.
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