Molecular glues for protein-protein interactions: Progressing toward a new dream.
Cell Chem Biol
; 31(6): 1064-1088, 2024 Jun 20.
Article
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| MEDLINE
| ID: mdl-38701786
ABSTRACT
The modulation of protein-protein interactions with small molecules is one of the most rapidly developing areas in drug discovery. In this review, we discuss advances over the past decade (2014-2023) focusing on molecular glues (MGs)-monovalent small molecules that induce proximity, either by stabilizing native interactions or by inducing neomorphic interactions. We include both serendipitous and rational discoveries and describe the different approaches that were used to identify them. We classify the compounds in three main categories degradative MGs, non-degradative MGs or PPI stabilizers, and MGs that induce self-association. Diverse, illustrative examples with structural data are described in detail, emphasizing the elements of molecular recognition and cooperative binding at the interface that are fundamental for a MG mechanism of action.
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MEDLINE
Asunto principal:
Unión Proteica
/
Proteínas
Idioma:
En
Revista:
Cell Chem Biol
Año:
2024
Tipo del documento:
Article