title: Amide-substituted farnesylcysteine analogs as inhibitors of human isoprenylcysteine carboxyl methyltransferase.
abstract: 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 microM.
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Donelson
authors.forename: Heather B
authors.initials: HB
authors.lastname: Hodges
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Macdougall
authors.forename: Brian S
authors.initials: BS
authors.lastname: Henriksen
authors.forename: Christine A
authors.initials: CA
authors.lastname: Hrycyna
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
mesh_terms: D000577:Amides / Q000737:chemistry; D020816:Amino Acid Motifs; D002462:Cell Membrane / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D003545:Cysteine / Q000737:chemistry*; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D011496:Protein Methyltransferases / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D000577:Amides; D011496:Protein Methyltransferases; C056501:protein-S-isoprenylcysteine O-methyltransferase; D003545:Cysteine