Lipid and sulfur substituted prenylcysteine analogs as human Icmt inhibitors |
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Authors: | Bergman Joel A Hahne Kalub Hrycyna Christine A Gibbs Richard A |
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Affiliation: | Department of Medicinal Chemistry and Molecular Pharmacology and Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA. |
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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. |
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