Antiangiogenic Activity and in Silico Cereblon Binding Analysis of Novel Thalidomide Analogs.
Molecules
; 25(23)2020 Dec 02.
Article
em En
| MEDLINE
| ID: mdl-33276504
ABSTRACT
Due to its antiangiogenic and anti-immunomodulatory activity, thalidomide continues to be of clinical interest despite its teratogenic actions, and efforts to synthesize safer, clinically active thalidomide analogs are continually underway. In this study, a cohort of 27 chemically diverse thalidomide analogs was evaluated for antiangiogenic activity in an ex vivo rat aorta ring assay. The protein cereblon has been identified as the target for thalidomide, and in silico pharmacophore analysis and molecular docking with a crystal structure of human cereblon were used to investigate the cereblon binding abilities of the thalidomide analogs. The results suggest that not all antiangiogenic thalidomide analogs can bind cereblon, and multiple targets and mechanisms of action may be involved.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Aorta
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Talidomida
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Neovascularização Fisiológica
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Inibidores da Angiogênese
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Ubiquitina-Proteína Ligases
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Proteínas Adaptadoras de Transdução de Sinal
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Simulação de Acoplamento Molecular
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article