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ID: ALA1770082

Journal: Bioorg Med Chem Lett

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

Authors: Majmudar JD, Hahne K, Hrycyna CA, Gibbs RA.

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.

CiteXplore: 21334890

DOI: 10.1016/j.bmcl.2011.01.078