Progress in 11ß-HSD1 inhibitors for the treatment of metabolic diseases: A comprehensive guide to their chemical structure diversity in drug development.
Eur J Med Chem
; 191: 112134, 2020 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-32088493
ABSTRACT
11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is a key metabolic enzyme that catalyzing the intracellular conversion of inactive glucocorticoids to physiologically active ones. Work over the past decade has demonstrated the aberrant overexpression of 11ß-HSD1 contributed to the pathophysiological process of metabolic diseases like obesity, type 2 diabetes mellitus, and metabolic syndromes. The inhibition of 11ß-HSD1 represented an attractive therapeutic strategy for the treatment of metabolic diseases. Therefore, great efforts have been devoted to developing 11ß-HSD1 inhibitors based on the diverse molecular scaffolds. This review focused on the structural features of the most important 11ß-HSD1 inhibitors and categorized them into natural products derivatives and synthetic compounds. We also briefly discussed the optimization process, binding modes, structure-activity relationships (SAR) and biological evaluations of each inhibitor. Moreover, the challenges and directions for 11ß-HSD1 inhibitors were discussed, which might provide some useful clues to guide the future discovery of novel 11ß-HSD1 inhibitors.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Produtos Biológicos
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11-beta-Hidroxiesteroide Desidrogenase Tipo 1
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Inibidores Enzimáticos
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Desenvolvimento de Medicamentos
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Doenças Metabólicas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article