Design of a novel long-acting dual GLP-1/GIP receptor agonist.
Bioorg Med Chem
; 100: 117630, 2024 Feb 15.
Article
en En
| MEDLINE
| ID: mdl-38330849
ABSTRACT
Tirzepatide, the first approved dual GLP-1/GIP receptor agonist (RA), has achieved better clinical outcomes than other GLP-1RAs. However, it is an imbalanced dual GIP/GLP-1 RA, and it remains unclear whether the degree of imbalance is optimal. Here, we present a novel long-acting dual GLP-1/GIP RA that exhibits better activity than tirzepatide toward GLP-1R. A candidate conjugate, D314, identified via peptide design, synthesis, conjugation, and experimentation, was evaluated using chronic studies in db/db and diet induced obese (DIO) mice. D314 achieved favorable blood glucose and body weight-lowering effects, equal to those of tirzepatide. Its half-life in dogs (T1/2 78.3 ± 14.01 h) reveals its suitability for once-weekly administration in humans. This preclinical study suggests the potential role of D314 as an effective agent for treating T2DM and obesity.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Receptores de la Hormona Gastrointestinal
/
Diabetes Mellitus Tipo 2
/
Péptido 1 Similar al Glucagón
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China