University of Oulu

Nathubhai, A., Haikarainen, T., Koivunen, J., Murthy, S., Koumanov, F., Lloyd, M., Holman, G., Pihlajaniemi, T., Tosh, D., Lehtiö, L., Threadgill, M. (2017) Highly Potent and Isoform Selective Dual Site Binding Tankyrase/Wnt Signaling Inhibitors That Increase Cellular Glucose Uptake and Have Antiproliferative Activity. Journal of Medicinal Chemistry 60(2): 814-820. doi:10.1021/acs.jmedchem.6b01574

Highly potent and isoform selective dual site binding tankyrase/Wnt signaling inhibitors that increase cellular glucose uptake and have antiproliferative activity

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Author: Nathubhai, Amit1; Haikarainen, Teemu2; Koivunen, Jarkko2;
Organizations: 1Drug and Target Discovery, Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, U. K.
2Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, PO Box 5400, 90014 Oulu, Finland
3Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, U. K.
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 0.6 MB)
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Language: English
Published: American Chemical Society, 2017
Publish Date: 2017-12-16


Compounds 𝟏𝟑 and 𝟏𝟒 were evaluated against eleven PARP isoforms to reveal that both 𝟏𝟑 and 𝟏𝟒 were more potent and isoform-selective towards inhibiting tankyrases (TNKSs) than the “standard” inhibitor 𝟏 (XAV939)⁵, i.e. IC₅₀ = 100 pM vs. TNKS2 and IC₅₀ = 6.5 μM vs. PARP1 for 𝟏𝟒. In cellular assays, 𝟏𝟑 and 𝟏𝟒 inhibited Wnt-signaling, enhanced insulin-stimulated glucose uptake and inhibited the proliferation of DLD-1 colorectal adenocarcinoma cells to a greater extent than 𝟏.

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Series: Journal of medicinal chemistry
ISSN: 0022-2623
ISSN-E: 1520-4804
ISSN-L: 0022-2623
Volume: 60
Issue: 2
Pages: 814 - 820
DOI: 10.1021/acs.jmedchem.6b01574
Type of Publication: A1 Journal article – refereed
Field of Science: 317 Pharmacy
Funding: The research was funded by Worldwide Cancer Research (Grant No. 13-1021 to AN, MDL, DT and MDT), MRC UK (Grant No. MR/J003417/1) to FK and GDH), Biocenter Oulu, Academy of Finland (287063 and 294085 to LL and TH) and the Center of Excellence Grant 2012-2017 of the Academy of Finland (284605 to TP)
Academy of Finland Grant Number: 287063
Detailed Information: 287063 (Academy of Finland Funding decision)
294085 (Academy of Finland Funding decision)
284605 (Academy of Finland Funding decision)
Copyright information: © 2016 American Chemical Society. Published in this repository with the kind permission of the publisher.