Jaimeen Majmudar - Probing the isoprenylcysteine carboxyl methyltransferase (Icmt) binding pocket: Sulfonamide modified farnesyl cysteine (SMFC) analogs as Icmt inhibitors

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  Publication Details (including relevant citation   information):

  Bioorganic &   Medicinal Chemistry Letters

  Volume 21, Issue 9, 1 May 2011, Pages   2616-2620


    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.

  Address (URL): http://www.sciencedirect.com/science/article/pii/S0960894X11001016