Identification of natural product inhibitors of PTP1B based on high-throughput virtual screening strategy: In silico, in vitro and in vivo studies.
Int J Biol Macromol
; 243: 125292, 2023 Jul 15.
Article
en En
| MEDLINE
| ID: mdl-37302637
ABSTRACT
Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of the insulin signaling pathway, which is a potential therapeutic target for the treatment of type 2 diabetes mellitus (T2DM). In this study, we identified several PTP1B inhibitors with high activity by using high-throughput virtual screening and in vitro enzyme inhibition activity verification strategies. Among them, baicalin was first reported as a selective mixed inhibitor of PTP1B, with IC50 value of 3.87 ± 0.45 µM, and its inhibitory activity against homologous proteins TCPTP, SHP2, and SHP1 exceeded 50 µM. Molecular docking study found that baicalin and PTP1B could bind stably, and revealed that baicalin had a dual inhibitory effect. Cell experiments showed that baicalin was almost non-toxic and could significantly enhance the phosphorylation of IRS-1 in C2C12 myotube cells. Animal experiments showed that baicalin could significantly reduce the blood sugar of STZ-induced diabetic mice models, and had a liver protective effect. In conclusion, this study can provide new ideas for the development of PTP1B selective inhibitors.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Diabetes Mellitus Experimental
/
Diabetes Mellitus Tipo 2
Tipo de estudio:
Diagnostic_studies
/
Screening_studies
Límite:
Animals
Idioma:
En
Revista:
Int J Biol Macromol
Año:
2023
Tipo del documento:
Article