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3-carboxy-4(1H)-quinolones

This CK2 inhibitors were revealed and evaluated to be a CK2 inhibitors after receptor-based virtual screening (docking) of around 70,000 compounds, coming from the Otava compound library. In vitro tests have shown that 4-oxo-1,4-dihydrobenzo[h]quinoline-3-carboxylic acid (Quinolone 9) is one of the most potent compounds of the series (IC50 value 1.0 µM). Kinetic studies showed that this compound is ATP competitive (Kі value is 0.28 µM).

Figure 1. The binding mode of Quinolone 9 in the CK2 active site. Hydrogen bonds are shown by the dotted lines.
Figure 1. The binding mode of Quinolone 9 in the CK2 active site. Hydrogen bonds are shown by the dotted lines.

Evaluation of the inhibitors on seven protein kinases shows considerable selectivity toward CK2. According to theoretical calculations and experimental data (docking and molecular dynamics simulation experiments), a structural model describing the key features of 3-carboxy-4(1H)-quinolones responsible for tight binding to CK2 active site has been developed. The identified inhibitors may be of interest for further structural optimization and biological evaluation.

  • Evaluation of 3-carboxy-4(1H)-quinolones as inhibitors of human protein kinase CK2. Golub AG, Yakovenko OY, Bdzhola VG, Sapelkin VM, Zien P, Yarmoluk SM. Mol Cell Biochem. J Med Chem. 2006, 49(22): 6443-6450.
  • Pat.: UА68984 А, C07D215/00, 2004-08-16. Application of 4-substituted 3-carboxyquinolines as protein kinase CK2 inhibitors. Sapelkin V.M., Lukashov S.S., Golub A.G., Bdzhola V.G., Yakovenko O.Ya., Yarmoluk S.M., Dubinina G.G.

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