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Lipid and sulfur substituted prenylcysteine analogs as human Icmt inhibitors.

ABSTRACT: Inhibition of isoprenylcysteine carboxyl methyltransferase (Icmt) offers a promising strategy for K-Ras driven cancers. We describe the synthesis and inhibitory activity of substrate-based analogs derived from several novel scaffolds. Modifications of both the prenyl group and thioether of N-acetyl-S-farnesyl-L-cysteine (AFC), a substrate for human Icmt (hIcmt), have resulted in low micromolar inhibitors of Icmt and have given insights into the nature of the prenyl binding site of hIcmt.

SUBMITTER: Bergman JA

PROVIDER: S-EPMC4037158 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Lipid and sulfur substituted prenylcysteine analogs as human Icmt inhibitors.

Bergman Joel A JA Hahne Kalub K Hrycyna Christine A CA Gibbs Richard A RA

Bioorganic & medicinal chemistry letters 20110621 18

Inhibition of isoprenylcysteine carboxyl methyltransferase (Icmt) offers a promising strategy for K-Ras driven cancers. We describe the synthesis and inhibitory activity of substrate-based analogs derived from several novel scaffolds. Modifications of both the prenyl group and thioether of N-acetyl-S-farnesyl-L-cysteine (AFC), a substrate for human Icmt (hIcmt), have resulted in low micromolar inhibitors of Icmt and have given insights into the nature of the prenyl binding site of hIcmt. ...[more]

PMID: 21782433

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