Highly Potent and Isoform Selective Dual Site Binding Tankyrase/Wnt Signaling Inhibitors That Increase Cellular Glucose Uptake and Have Antiproliferative Activity

Nathubhai, Amit, Haikarainen, T., Koivunen, J., Murthy, S., Koumanov, F., Lloyd, M.D., Holman, J.D., Pihlajaniemi, T., Tosh, D., Lehtiö, L. and Threadgill, M.D. (2016) 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). pp. 814-820. ISSN 0022-2623

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Abstract

Compounds 13 and 14 were evaluated against 11 PARP isoforms to reveal that both 13 and 14 were more potent
and isoform selective toward 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.

Item Type: Article
Subjects: Sciences > Chemistry
Sciences
Divisions: Health Sciences and Wellbeing Beacon > Drug Discovery and Application Workstream
Depositing User: Amit Nathubhai
Date Deposited: 10 Aug 2018 08:24
Last Modified: 10 Aug 2018 08:24
URI: http://sure.sunderland.ac.uk/id/eprint/9787

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