|
|||||
|
|
Probing the isoprenylcysteine carboxyl methyltransferase (Icmt) binding pocket: sulfonamide modified farnesyl cysteine (SMFC) analogs as Icmt inhibitors |
|
| Authors: | Majmudar Jaimeen D Hahne Kalub Hrycyna Christine A Gibbs Richard A |
| Affiliation: | a Department of Medicinal Chemistry and Molecular Pharmacology and the Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA b Department of Chemistry and the Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA |
| Abstract: | Human isoprenylcysteine carboxyl methyltransferase (hIcmt) is a promising anticancer target as it is important for the post-translational modification of oncogenic Ras proteins. We herein report the synthesis and biochemical activity of 41 farnesyl-cysteine based analogs versus hIcmt. We have demonstrated that the amide linkage of a hIcmt substrate can be replaced by a sulfonamide bond to achieve hIcmt inhibition. The most potent sulfonamide-modified farnesyl cysteine analog was 6ag with an IC50 of 8.8 ± 0.5 μM for hIcmt. |
| Keywords: | Inhibitor Methyltransferase Enzymes Isoprenoid Signal transduction Anti-cancer agents |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ | |