Discovery of potent, reversible MetAP2 inhibitors via fragment based drug discovery and structure based drug design-Part 1.
Bioorg Med Chem Lett
; 26(12): 2774-2778, 2016 Jun 15.
Article
em En
| MEDLINE
| ID: mdl-27155900
ABSTRACT
Methionine aminopeptidase 2 (MetAP2) is an enzyme that cleaves an N-terminal methionine residue from a number of newly synthesized proteins. Pre-clinical and clinical studies suggest that MetAP2 inhibitors could be used as a novel treatment for obesity. Herein we describe our use of fragment screening methods and structural biology to quickly identify and elaborate an indazole fragment into a series of reversible MetAP2 inhibitors with <10nM potency, excellent selectivity, and favorable in vitro safety profiles.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peso Corporal
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Glicoproteínas
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Inibidores Enzimáticos
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Descoberta de Drogas
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Aminopeptidases
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Indazóis
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Obesidade
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article