A novel tankyrase small-molecule inhibitor suppresses APC mutation-driven colorectal tumor growth
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F13%3A00423239" target="_blank" >RIV/68378050:_____/13:00423239 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1158/0008-5472.CAN-12-4562" target="_blank" >http://dx.doi.org/10.1158/0008-5472.CAN-12-4562</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1158/0008-5472.CAN-12-4562" target="_blank" >10.1158/0008-5472.CAN-12-4562</a>
Alternative languages
Result language
angličtina
Original language name
A novel tankyrase small-molecule inhibitor suppresses APC mutation-driven colorectal tumor growth
Original language description
Most colorectal cancers (CRC) are initiated by mutations of APC, leading to increased ?-catenin-mediated signaling. However, continued requirement of Wnt/?-catenin signaling for tumor progression in the context of acquired KRAS and other mutations is less well-established. To attenuate Wnt/?-catenin signaling in tumors, we have developed potent and specific small-molecule tankyrase inhibitors, G007-LK and G244-LM, that reduce Wnt/?-catenin signaling by preventing poly(ADP-ribosyl)ation-dependent AXIN degradation, thereby promoting ?-catenin destabilization. We show that novel tankyrase inhibitors completely block ligand-driven Wnt/?-catenin signaling in cell culture and display approximately 50% inhibition of APC mutation-driven signaling in most CRC cell lines. It was previously unknown whether the level of AXIN protein stabilization by tankyrase inhibition is sufficient to impact tumor growth in the absence of normal APC activity. Compound G007-LK displays favorable pharmacokinetic p
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
EB - Genetics and molecular biology
OECD FORD branch
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Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2013
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cancer Research
ISSN
0008-5472
e-ISSN
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Volume of the periodical
73
Issue of the periodical within the volume
10
Country of publishing house
US - UNITED STATES
Number of pages
13
Pages from-to
3132-3144
UT code for WoS article
000318903700021
EID of the result in the Scopus database
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