Amide-substituted farnesylcysteine analogs as inhibitors of human isoprenylcysteine carboxyl methyltransferase

N-Acetyl- S-farnesyl- l-cysteine (AFC) is the minimal substrate for the enzyme isoprenylcysteine carboxyl methyltransferase (Icmt). A series of amide-modified farnesylcysteine analogs were synthesized and screened against human Icmt. From a 23-membered library of compounds, six inhibitors were ident...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2006-08, Vol.16 (16), p.4420-4423
Main Authors: Donelson, James L., Hodges, Heather B., MacDougall, Daniel D., Henriksen, Brian S., Hrycyna, Christine A., Gibbs, Richard A.
Format: Article
Language:English
Subjects:
Amides - chemistry
Amino Acid Motifs
Biological and medical sciences
Cell Membrane - metabolism
Chemistry, Pharmaceutical
Cysteine - chemistry
Drug Design
Farnesylcysteine analogs
Humans
Inhibitory Concentration 50
Isoprenylcysteine carboxyl methyltransferase
Medical sciences
Miscellaneous
Models, Chemical
Pharmacology. Drug treatments
Post-translational modification
Protein Methyltransferases - antagonists & inhibitors
Protein Methyltransferases - chemistry
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Summary:N-Acetyl- S-farnesyl- l-cysteine (AFC) is the minimal substrate for the enzyme isoprenylcysteine carboxyl methyltransferase (Icmt). A series of amide-modified farnesylcysteine analogs were synthesized and screened against human Icmt. From a 23-membered library of compounds, six inhibitors were identified and evaluated further. The adamantyl derivative 7c was the most potent inhibitor with an IC 50 of 12.4 μM.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2006.05.029