Designed dualsteric modulators: A novel route for drug discovery.
Drug Discov Today
; 29(10): 104141, 2024 Oct.
Article
in En
| MEDLINE
| ID: mdl-39168404
ABSTRACT
Orthosteric and allosteric modulators, which constitute the majority of current drugs, bind to the orthosteric and allosteric sites of target proteins, respectively. However, the clinical efficacy of these agents is frequently compromised by poor selectivity or reduced potency. Dualsteric modulators feature two linked pharmacophores that bind to orthosteric and allosteric sites of the target proteins simultaneously, thereby offering a promising avenue to achieve both potency and specificity. In this review, we summarize recent structures available for dualsteric modulators in complex with their target proteins, elucidating detailed drug-target interactions and dualsteric action patterns. Moreover, we provide a design and optimization strategy for dualsteric modulators based on structure-based drug design approaches.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Drug Design
/
Allosteric Site
/
Drug Discovery
Limits:
Animals
/
Humans
Language:
En
Journal:
Drug Discov Today
Journal subject:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Year:
2024
Document type:
Article
Country of publication:
Reino Unido