Structural Genomics Consortium, Johann Wolfgang Goethe University, Buchmann Institute for Molecular Life Sciences, Max-von-Laue-Straße 15 , D-60438 Frankfurt am Main , Germany.
Institute for Pharmaceutical Chemistry , Johann Wolfgang Goethe University , Max-von-Laue-Straße 9 , D-60438 Frankfurt am Main , Germany.
J Med Chem. 2019 Mar 14;62(5):2830-2836. doi: 10.1021/acs.jmedchem.8b01213. Epub 2019 Feb 26.
We describe SGC-GAK-1 (11), a potent, selective, and cell-active inhibitor of cyclin G-associated kinase (GAK), together with a structurally related negative control SGC-GAK-1N (14). 11 was highly selective in an in vitro kinome-wide screen, but cellular engagement assays defined RIPK2 as a collateral target. We identified 18 as a potent RIPK2 inhibitor lacking GAK activity. Together, this chemical probe set can be used to interrogate GAK cellular biology.
我们描述了 SGC-GAK-1（11），这是一种有效的、选择性的、细胞活性的细胞周期蛋白 G 相关激酶（GAK）抑制剂，以及一个结构相关的负对照 SGC-GAK-1N（14）。11 在体外激酶组广泛筛选中具有高度选择性，但细胞结合测定将 RIPK2 定义为一个附带靶点。我们鉴定出 18 是一种有效的、缺乏 GAK 活性的 RIPK2 抑制剂。总的来说，这个化学探针集可用于研究 GAK 的细胞生物学。
