Amide-modified prenylcysteine based Icmt inhibitors: Structure–activity relationships, kinetic analysis and cellular characterization

JD Majmudar, HB Hodges-Loaiza, K Hahne…

Index: Majmudar, Jaimeen D.; Hodges-Loaiza, Heather B.; Hahne, Kalub; Donelson, James L.; Song, Jiao; Shrestha, Liza; Harrison, Marietta L.; Hrycyna, Christine A.; Gibbs, Richard A. Bioorganic and Medicinal Chemistry, 2012 , vol. 20, # 1 p. 283 - 295

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Citation Number: 11

Abstract

Human protein isoprenylcysteine carboxyl methyltransferase (hIcmt) is the enzyme responsible for the α-carboxyl methylation of the C-terminal isoprenylated cysteine of CaaX proteins, including Ras proteins. This specific posttranslational methylation event has been shown to be important for cellular transformation by oncogenic Ras isoforms. This finding led to interest in hIcmt inhibitors as potential anti-cancer agents. Previous analog studies ...