• In Silico Evaluation of Apilimod Targeting MMP-9 in Pancreatic Cancer
  • Artemis Azad Aza,1,* Elena Ebrahimian,2 Masoud Homayouni Tabrizi ,3
    1. Department of Biology, Faculty of Basic Sciences, Mashhad Branch, Islamic Azad University, Mashhad, Iran
    2. Department of Biology, Faculty of Basic Sciences, Mashhad Branch, Islamic Azad University, Mashhad, Iran
    3. Department of Biology, Ma.C., Islamic Azad University, Mashhad, Iran


  • Introduction: Matrix metalloproteinase-9 (MMP-9) is involved in extracellular matrix remodeling and contributes to tumor invasion and metastasis in pancreatic cancer. Apilimod, an inhibitor of the lipid kinase PIKfyve, has emerged as a potential therapeutic candidate in oncology models. Here, molecular docking was employed to computationally evaluate whether apilimod can bind to MMP-9 and thereby potentially inhibit its activity (in silico), assessing the compound’s prospective relevance for pancreatic cancer therapy. These in-silico results require further validation by molecular-dynamics simulations and biochemical/cellular assays.
  • Methods: The receptor, which is MMP-9, was downloaded from RCSB PDB (PDB ID: 1L6J) and prepared using PyMOL. The apilimod ligand was also downloaded from PubChem (CID: 10173277). Both were prepared in AutoDockTools. Docking was performed using AutoDockVina. Ultimately, the best conformation was selected based on the lowest binding energy, and its complex with the receptor was analyzed through the PLIP website to determine the binding site based on the type and residue numbers of the interactions and the binding strength based on the type and number of interactions. These results were also visualized in PyMOL.
  • Results: PLIP analysis revealed three hydrophobic interactions between apilimod and GLU416, LEU418, and ARG424. Also, three hydrogen bonds with apilimod and GLU416, one hydrogen bond with apilimod MET423, and two hydrogen bonds with ARG424 indicated a relatively strong interaction. And there was a π-Cation Interactions with ARG424.
  • Conclusion: In summary, Due to the low binding energy, favorable docking score, and strong interactions between apilimod and MMP-9 protein, apilimod may serve as a inhibitor candidate for MMP-9 in the treatment of pancreatic cancer. However, Apilimod emerges as a potential MMP-9 inhibitor candidate, but experimental confirmation (in vitro and in vivo) is required to establish inhibitory activity and therapeutic relevance in pancreatic cancer.
  • Keywords: MMP-9, Apilimod, Molecular Docking, Pancreatic Cancer.