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

Amit Nathubhai, Teemu Haikarainen, Jarkko Koivunen, Sudarshan Murthy, Francoise Koumanov, Matthew Lloyd, Geoffrey Holman, Taina Pihlajaniemi, David Tosh, Lari Lehtio, Michael Threadgill

Research output: Contribution to journalArticle

28 Citations (Scopus)
148 Downloads (Pure)

Abstract

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.
Original languageEnglish
Pages (from-to)814-820
Number of pages7
JournalJournal of Medicinal Chemistry
Volume60
Issue number2
Early online date16 Dec 2016
DOIs
Publication statusPublished - 26 Jan 2017

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