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Bioorg Med Chem Lett. 2011 May 1;21(9):2616-20. doi: 10.1016/j.bmcl.2011.01.078. Epub 2011 Jan 22.

Probing the isoprenylcysteine carboxyl methyltransferase (Icmt) binding pocket: sulfonamide modified farnesyl cysteine (SMFC) analogs as Icmt inhibitors.

Author information

1
Department of Medicinal Chemistry and Molecular Pharmacology 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 IC(50) of 8.8±0.5 μM for hIcmt.

PMID:
21334890
PMCID:
PMC3401633
DOI:
10.1016/j.bmcl.2011.01.078
[Indexed for MEDLINE]
Free PMC Article

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