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.