设计一组细胞周期蛋白 G 相关激酶（GAK）/表皮生长因子受体（EGFR）抑制剂，以研究脊索瘤中 EGFR 和 GAK 的关系。
Design of a Cyclin G Associated Kinase (GAK)/Epidermal Growth Factor Receptor (EGFR) Inhibitor Set to Interrogate the Relationship of EGFR and GAK in Chordoma.
机构信息
Structural Genomics Consortium, UNC Eshelman School of Pharmacy , University of North Carolina at Chapel Hill , Chapel Hill , North Carolina 27599 , United States.
Department of Pharmacology, School of Medicine , University of North Carolina at Chapel Hill , Chapel Hill , North Carolina 27599 , United States.
出版信息
J Med Chem. 2019 May 9;62(9):4772-4778. doi: 10.1021/acs.jmedchem.9b00350. Epub 2019 Apr 19.
We describe the design of a set of inhibitors to investigate the relationship between cyclin G associated kinase (GAK) and epidermal growth factor receptor (EGFR) in chordoma bone cancers. These compounds were characterized both in vitro and using in cell target engagement assays. The most potent chordoma inhibitors were further characterized in a kinome-wide screen demonstrating narrow spectrum profiles. While we observed a direct correlation between EGFR and antiproliferative effects on chordoma, GAK inhibition appeared to have only a limited effect.
我们设计了一组抑制剂来研究脊索瘤骨癌中细胞周期 G 相关激酶（GAK）和表皮生长因子受体（EGFR）之间的关系。这些化合物在体外和细胞内靶标结合测定中都进行了特征描述。最有效的脊索瘤抑制剂在激酶组全谱筛选中进一步进行了特征描述，显示出狭窄的谱型。虽然我们观察到 EGFR 与脊索瘤的抗增殖作用之间存在直接相关性，但 GAK 抑制似乎只有有限的作用。
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