Virtual and in Vitro Screening Employing a Repurposing Approach Reveal 13-cis-Retinoic Acid is a PTP1B Inhibitor.
ChemMedChem
; : e202400452, 2024 Aug 07.
Article
in En
| MEDLINE
| ID: mdl-39113101
ABSTRACT
Current treatments for type 2 diabetes (T2D) mainly rely on exercise, dietary control, and anti-diabetic drugs to enhance insulin secretion and improve insulin sensitivity. However, there is a need for more therapeutic options, as approved drugs targeting different pharmacological objectives are still unavailable. One potential target that has attracted attention is the protein tyrosine phosphatase 1B (PTP1B), which negatively regulates the insulin signaling pathway. In this work, a comprehensive computational screening was carried out using cheminformatics and molecular docking on PTP1B, employing a rigorous repurposing approach. The screening involved approved drugs and compounds under research as anti-diabetics that bind to targets such as peroxisome proliferator-activated receptor gamma (PPAR-γ) and α-glucosidase. Several computational hits were then meticulously tested inâ
vitro against PTP1B, with 13-cis-retinoic acid (3a) showing an IC50 of 0.044â
mM and competitive inhibition. Molecular dynamics studies further confirmed that 3a can bind to the catalytic binding site of PTP1B. Finally, 3a is the first time it has been reported as an inhibitor of PTP1B, making it a potentially valuable candidate for further studies in D2T treatment.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
ChemMedChem
Journal subject:
FARMACOLOGIA
/
QUIMICA
Year:
2024
Document type:
Article
Country of publication:
Germany