Fragment-based discovery of focal adhesion kinase inhibitors.
Bioorg Med Chem Lett
; 23(19): 5401-9, 2013 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-23973211
ABSTRACT
Chemically diverse fragment hits of focal adhesion kinase (FAK) were discovered by surface plasmon resonance (SPR) screening of our in-house fragment library. Site specific binding of the primary hits was confirmed in a competition setup using a high-affinity ATP-site inhibitor of FAK. Protein crystallography revealed the binding mode of 41 out of 48 selected fragment hits within the ATP-site. Structural comparison of the fragment binding modes with a DFG-out inhibitor of FAK initiated first synthetic follow-up optimization leading to improved binding affinity.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
/
Sulfonamidas
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Proteína-Tirosina Quinases de Adesão Focal
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Bibliotecas de Moléculas Pequenas
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Descoberta de Drogas
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Indóis
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Alemanha