Allosteric inhibitor of ß-catenin selectively targets oncogenic Wnt signaling in colon cancer.
Sci Rep
; 10(1): 8096, 2020 05 15.
Article
in En
| MEDLINE
| ID: mdl-32415084
ABSTRACT
Abnormal regulation of ß-catenin initiates an oncogenic program that serves as a main driver of many cancers. Albeit challenging, ß-catenin is an attractive drug target due to its role in maintenance of cancer stem cells and potential to eliminate cancer relapse. We have identified C2, a novel ß-catenin inhibitor, which is a small molecule that binds to a novel allosteric site on the surface of ß-catenin. C2 selectively inhibits ß-catenin, lowers its cellular load and significantly reduces viability of ß-catenin-driven cancer cells. Through direct binding to ß-catenin, C2 renders the target inactive that eventually activates proteasome system for its removal. Here we report a novel pharmacologic approach for selective inhibition of ß-catenin via targeting a cryptic allosteric modulation site. Our findings may provide a new perspective for therapeutic targeting of ß-catenin.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Neoplastic Stem Cells
/
Beta Catenin
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Small Molecule Libraries
/
Wnt Signaling Pathway
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Neoplasms
/
Antineoplastic Agents
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Sci Rep
Year:
2020
Document type:
Article
Affiliation country:
United States