Department für Chemie, Institut für Biochemie, Universität zu Köln, Zülpicher Str. 47, D-50674 Köln, Germany.
Institut für Pharmazeutische und Medizinische Chemie, Westfälische Wilhelms-Universität Münster, PharmaCampus, Corrensstr. 48, D-48149 Münster, Germany.
J Med Chem. 2020 Jul 23;63(14):7766-7772. doi: 10.1021/acs.jmedchem.0c00587. Epub 2020 Jul 14.
Selective inhibitors of protein kinase CK2 with significant cytotoxicity on tumor cells based on a 2-aminothiazole scaffold were described recently. Here, these studies are supplemented with representative CK2α/CK2α' complex structures. They reveal that the 2-aminothiazole-based inhibitors occupy the ATP cavity, whereas preliminary data had indicated an allosteric binding site. The crystal structure findings are corroborated by subsequent enzyme kinetic studies; their atomic-resolution quality provides the basis for future optimization of these promising CK2 inhibitors.
最近有报道称，基于 2-氨基噻唑骨架的蛋白激酶 CK2 选择性抑制剂对肿瘤细胞具有显著的细胞毒性。在此基础上，本研究补充了具有代表性的 CK2α/CK2α' 复合物结构。结果表明，基于 2-氨基噻唑的抑制剂占据了 ATP 腔，而初步数据表明存在变构结合位点。晶体结构研究结果得到了后续酶动力学研究的证实；其原子分辨率的质量为这些有前途的 CK2 抑制剂的进一步优化提供了基础。
