脂类和硫取代的异戊烯基半胱氨酸类似物作为人 Icmt 抑制剂。
Lipid and sulfur substituted prenylcysteine analogs as human Icmt inhibitors.
机构信息
Department of Medicinal Chemistry and Molecular Pharmacology and Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA.
出版信息
Bioorg Med Chem Lett. 2011 Sep 15;21(18):5616-9. doi: 10.1016/j.bmcl.2011.06.053. Epub 2011 Jun 21.
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.
摘要
异戊烯基半胱氨酸羧甲基转移酶（Icmt）的抑制为 K-Ras 驱动的癌症提供了一种有前途的策略。我们描述了几种新型支架衍生的基于底物的类似物的合成和抑制活性。对 N-乙酰-S-法呢基-L-半胱氨酸（AFC）的 prenyl 基团和硫醚进行修饰，AFC 是人类 Icmt（hIcmt）的底物，得到了对 Icmt 的低微摩尔抑制剂，并深入了解了 hIcmt 的 prenyl 结合位点的性质。
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