Motif mediated protein-protein interactions as drug targets.
Cell Commun Signal
; 14: 8, 2016 Mar 02.
Article
em En
| MEDLINE
| ID: mdl-26936767
ABSTRACT
Protein-protein interactions (PPI) are involved in virtually every cellular process and thus represent an attractive target for therapeutic interventions. A significant number of protein interactions are frequently formed between globular domains and short linear peptide motifs (DMI). Targeting these DMIs has proven challenging and classical approaches to inhibiting such interactions with small molecules have had limited success. However, recent new approaches have led to the discovery of potent inhibitors, some of them, such as Obatoclax, ABT-199, AEG-40826 and SAH-p53-8 are likely to become approved drugs. These novel inhibitors belong to a wide range of different molecule classes, ranging from small molecules to peptidomimetics and biologicals. This article reviews the main reasons for limited success in targeting PPIs, discusses how successful approaches overcome these obstacles to discovery promising inhibitors for human protein double minute 2 (HDM2), B-cell lymphoma 2 (Bcl-2), X-linked inhibitor of apoptosis protein (XIAP), and provides a summary of the promising approaches currently in development that indicate the future potential of PPI inhibitors in drug discovery.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos Macrocíclicos
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Bibliotecas de Moléculas Pequenas
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Domínios e Motivos de Interação entre Proteínas
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Descoberta de Drogas
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Peptidomiméticos
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Mapas de Interação de Proteínas
Limite:
Animals
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Humans
Idioma:
En
Revista:
Cell Commun Signal
Ano de publicação:
2016
Tipo de documento:
Article