Spannhoff Astrid, Machmur Rospita, Heinke Ralf, Trojer Patrick, Bauer Ingo, Brosch Gerald, Schüle Roland, Hanefeld Wolfgang, Sippl Wolfgang, Jung Manfred
Institute of Pharmaceutical Sciences, Albert-Ludwigs-University of Freiburg, Germany.
Bioorg Med Chem Lett. 2007 Aug 1;17(15):4150-3. doi: 10.1016/j.bmcl.2007.05.088. Epub 2007 Jun 3.
Via virtual screening we identified a thioglycolic amide as an arginine methyltransferase (PRMT) inhibitor and tested it and related compounds against the fungal PRMT RmtA and human PRMT1. Compound RM65 was the most potent druglike inhibitor (IC(50)-PRMT1: 55.4 microM) and showed histone hypomethylation in HepG2 cells. Docking studies proposed binding at the substrate and SAM cofactor binding pocket. It may serve as a lead for further PRMT inhibitors useful for the treatment for hormone dependent cancers.
通过虚拟筛选，我们鉴定出一种巯基乙酸酰胺作为精氨酸甲基转移酶（PRMT）抑制剂，并针对真菌PRMT RmtA和人类PRMT1对其及相关化合物进行了测试。化合物RM65是最有效的类药物抑制剂（IC(50)-PRMT1：55.4 microM），并在HepG2细胞中显示出组蛋白低甲基化。对接研究表明其结合于底物和SAM辅因子结合口袋。它可能作为进一步开发用于治疗激素依赖性癌症的PRMT抑制剂的先导化合物。
