Inhibition of tankyrase by a novel small molecule significantly attenuates prostate cancer cell proliferation.
Cancer Lett
; 443: 80-90, 2019 02 28.
Article
en En
| MEDLINE
| ID: mdl-30472184
ABSTRACT
Tankyrase (TNKS) is a crucial mediator of Wnt signal transduction and has been recognized as a novel molecular target for Wnt-pathway dependent cancer. TNKS is stabilized by the ubiquitin-specific protease 25 (USP25). The effect of disruption of the interaction between TNKS and USP25 by small molecules on prostate cancer proliferation is unknown. In this study we conducted a hierarchical virtual screening with more than 200,000 compounds on the characterized structures of the USP25/TNKS-ARC5 protein complex. In silico analysis and in vitro validation revealed that a small molecule, called C44, binds to the protein-protein interaction (PPI) interface of TNKS and USP25. We show that C44 disrupts the interaction between TNKS and USP25 leading to a higher half-life of AXIN and the breakdown of Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Próstata
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Tanquirasas
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Inhibidores Enzimáticos
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Bibliotecas de Moléculas Pequeñas
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Cancer Lett
Año:
2019
Tipo del documento:
Article
País de afiliación:
China