Farnesyl-derived inhibitors of ras farnesyl transferase.
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.
Hoechst Marion Roussel, Inc., Cincinnati, Ohio 45215, USA.
M S
MS
Kang
D M
DM
Stemerick
J H
JH
Zwolshen
B S
BS
Harry
P S
PS
Sunkara
B L
BL
Harrison
D019883:Alkyl and Aryl Transferases; D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D015689:Oncogene Protein p21(ras) / Q000378:metabolism; D063065:Organophosphonates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017368:Protein Prenylation; D013329:Structure-Activity Relationship; D013552:Swine; D014166:Transferases / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D063065:Organophosphonates; D014166:Transferases; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase; D015689:Oncogene Protein p21(ras)