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Issue 2, 2017
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Discovery of new dual binding TNKS inhibitors of Wnt signaling inhibition by pharmacophore modeling, molecular docking and bioassay

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Abstract

Tankyrases (TNKS), key transmitters in the Wnt signaling pathway which is very conservative in evolution, are vital targets as they are overexpressed widely in many cancers. In this work, 5 inhibitors with novel structures have been discovered and validated using the ligand-based (pharmacophore) virtual screening, docking study, and Luciferase reporter assays for Wnt signaling. Among them, PYL-1, in particular, was the most potent inhibitor with an IC50 value of 9.56 μM against Wnt signaling. The analysis of binding modes was performed to further understand the vital interactions between inhibitors and TNKS 2, and the five hits belong to dual site inhibitors. This work could be helpful for the design and development of novel dual binders as TNKS inhibitors.

Graphical abstract: Discovery of new dual binding TNKS inhibitors of Wnt signaling inhibition by pharmacophore modeling, molecular docking and bioassay

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Supplementary files

Article information


Submitted
19 Oct 2016
Accepted
05 Dec 2016
First published
07 Dec 2016

Mol. BioSyst., 2017,13, 363-370
Article type
Paper

Discovery of new dual binding TNKS inhibitors of Wnt signaling inhibition by pharmacophore modeling, molecular docking and bioassay

Y. Pu, S. Zhang, Z. Chang, Y. Zhang, D. Wang, L. Zhang, Y. Li and Z. Zuo, Mol. BioSyst., 2017, 13, 363
DOI: 10.1039/C6MB00712K

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