Skip to content
2000
Volume 17, Issue 4
  • ISSN: 1573-4099
  • E-ISSN: 1875-6697

Abstract

Introduction: In many diseased states, especially fibrosis and cancer, TGF-β family members are overexpressed and the outcome of signaling is diverted toward disease progression. As the result of activin receptor-like kinase 1 (ALK1) plays a key role in TGF-β signaling, discovering inhibitors of ALK1 to block TGF-β signaling for a therapeutic benefit has become an effective strategy. Methods: In this work, ZINC15894217 and ZINC12404282 were identified as potential ALK1 inhibitors using molecular docking, molecular dynamics simulation and MM/PBSA calculations studies. The analysis of energy decomposition found that Val208, Val216, Lys229, Gly283, Arg334 and Leu337 acted as crucial residues for ligand binding and system stabilizing. Results: In addition, these compounds displayed excellent pharmacological and structural properties, which can be further evaluated through in vitro and in vivo experiments for the inhibition of ALK1 to be developed as drugs against fibrosis and tumor. Conclusion: Overall, our study illustrated a time- and cost-effective computer aided drug design procedure to identify potential ALK1 inhibitors. It would provide useful information for further development of ALK1 inhibitors to improve disease related to TGF-β signal pathway.

Loading

Article metrics loading...

/content/journals/cad/10.2174/1573409916666200628102315
2021-07-01
2025-05-23
Loading full text...

Full text loading...

/content/journals/cad/10.2174/1573409916666200628102315
Loading
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test