异吲哚
激酶
对接(动物)
蛋白激酶A
化学
DYRK1A型
生物化学
酶
酪蛋白激酶2
立体化学
丝裂原活化蛋白激酶激酶
医学
护理部
作者
Andriy G. Golub,O. S. Yakovenko,A.O. Prykhod'ko,S. S. Lukashov,Volodymyr G. Bdzhola,S. M. Yarmoluk
标识
DOI:10.1016/j.bbapap.2007.10.009
摘要
Protein kinase CK2 (Casein Kinase 2) is an extremely pleiotropic Ser/Thr kinase with high constitutive activity. The observation of CK2 deregulations in various pathological processes suggests that CK2 inhibitors may have a therapeutic value, particularly as anti-neoplastic and antiviral drugs. Here, we present the 4,5,6,7-tetrahalogeno-1H-isoindole-1,3(2H)-diones as a novel potent class of CK2 inhibitors. We identified this class of inhibitors by high-throughput docking of a compound collection in the ATP-binding site of human CK2. The most active compounds are 2-(4,5,6,7-tetraiodo-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propanoic acid and 2-(4,5,6,7-tetraiodo-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetic acid with IC50 values of 0.15 μM and 0.3 μM, respectively. These inhibitors are ATP-competitive and they only minimally inhibit the activities of protein kinases DYRK1a, MSK1, GSK3 and CDK5. Binding modes for the most active inhibitors are proposed.
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