Discovery of novel small molecule inhibitors of S100P with in vitro anti-metastatic effects on pancreatic cancer cells.
Eur J Med Chem
; 203: 112621, 2020 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-32707527
ABSTRACT
S100P, a calcium-binding protein, is known to advance tumor progression and metastasis in pancreatic and several other cancers. Herein is described the in silico identification of a putative binding pocket of S100P to identify, synthesize and evaluate novel small molecules with the potential to selectively bind S100P and inhibit its activation of cell survival and metastatic pathways. The virtual screening of a drug-like database against the S100P model led to the identification of over 100 clusters of diverse scaffolds. A representative test set identified a number of structurally unrelated hits that inhibit S100P-RAGE interaction, measured by ELISA, and reduce in vitro cell invasion selectively in S100P-expressing pancreatic cancer cells at 10 µM. This study establishes a proof of concept in the potential for rational design of small molecule S100P inhibitors for drug candidate development.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Desenho de Fármacos
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Proteínas S100
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Bibliotecas de Moléculas Pequenas
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Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Eur J Med Chem
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Reino Unido
País de publicação:
FR
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FRANCE
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FRANCIA
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FRANÇA