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Investigation of pharmacokinetic properties of CK2 Inhibitors with an Indeno[1,2-b]indole scaffold
* 1 , 2 , 1
1  Institute of Pharmaceutical and Medicinal Chemistry, Westfälische Wilhelms-Universität Münster
2  ISPB-Faculte de Pharmacie, Universite Claude Bernard Lyon 1, EA 4446 Bioactive Molecules and Medicinal Chemistry

Published: 30 October 2019 by MDPI in 5th International Electronic Conference on Medicinal Chemistry session ECMC-5

The highly pleiotropic and constitutively active protein kinase CK2 plays an important role in several cellular mechanisms. Due to its overexpression and elevated activity in tumor cells, CK2 became an important target in tumor therapy nowadays. It was shown, that the kinase causes antiapoptotic and proliferation enhancing effects in neoplastic tissues [1,2]. Moreover, the reduction of CK2 activity in tumor cells leads to apoptosis while normal cells stay unaffected [3].

Indeno[1,2-b]indoles are ATP competitive CK2 inhibitors with IC50 values in the nanomolar range of concentration. NA16 was described as one of the most potent indeno[1,2-b]indoles with an IC50 value of 25 nM [4]. Therefore, the pharmacokinetic properties of NA16 were further analyzed during this study. It could be shown that NA16 reduced the growth of different tumor cell lines and induced cancer cell apoptosis. Furthermore, its effect on HUVEC cell growth was comparable with the effect of CX-4945, a CK2 inhibitor in clinical trials [5], which was used as control. Intracellular concentrations of NA16 were higher than concentrations of CX-4945 at different time points. Metabolism studies showed that NA16 is moderate metabolic stable and is not glucuronidated. These results underline the potential of NA16 as an antitumor drug.


[1] Ahmed, K et al.: Trends Cell Biol 2002, 12, 226-230.
[2] Meggio, F. and Pinna, L.A.: FASEB J. 2003, 17, 349-368.
[3] Slaton, J. W. et al.: Mol Cancer Res 2004, 2, 172.
[4] Gozzi, G. J. et al.: J Med Chem 2015, 58, 265-277.
[5] Siddiqui-Jain, A. et al.: Cancer Res 2010, 70, 24.

Keywords: Protein kinase CK2; ATP-competitive inhibitor; cell culture; pharmcokinetic