Related Experiment Video
Updated: May 11, 2026
High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
Published on: November 9, 2020
Repurposed pharmacotherapy: targeting cathepsin L with repurposed drugs in virtual screening
Mohammad Khalid1, Mohammed H Alqarni2, Ahmed I Foudah2
1Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia. drkhalid8811@gmail.com.
Abstract:
Proteolytic enzymes are closely associated with cancer and are important in different phases, including tumor growth, angiogenesis, and metastasis. Despite efforts to target matrix metalloproteases (MMPs), clinical trials have often resulted in various side effects such as musculoskeletal pain, joint stiffness, and tendinitis, making them less optimal for chronic cancer treatment. Thus, there is a need for the identification of other protease targets that would provide different approaches towards the management of cancer. Of these targets, Cathepsin L (CatL) is a lysosomal cysteine protease that has been identified as a therapeutic target that is implicated in cancer development and metastasis. In this study, we performed an integrated approach of virtual screening and molecular dynamics (MD) simulations to identify the potential inhibitors of CatL from a library of drugs that have been used for different treatments. Towards this goal, we performed virtual screening of the DrugBank database and found two repurposed drugs, Irinotecan and Nilotinib, against CatL based on their docking profiles, favorable docking scores, and specific interaction with the CatL binding pocket. MD simulations of the Irinotecan and Nilotinib bound structures with CatL were carried out, and the analysis showed that both these compounds could function as CatL inhibitors as the protein-ligand interactions were stable for 300 ns. This study highlights the robustness of these drugs bound to CatL and indicates that they could be repurposed for the treatment of cancer. These findings endorse the use of computer-based approaches for the identification of new inhibitors, and the present study will be a useful resource for future experimental research towards the targeting of CatL in cancer therapeutics.
Insights
This study repurposed Irinotecan and Nilotinib as potential Cathepsin L (CatL) inhibitors for cancer treatment. Computational methods identified these drugs, showing stable interactions with CatL, offering new therapeutic avenues.
Area of Science:
- Biochemistry
- Computational Biology
- Oncology
Background:
- Proteolytic enzymes play a key role in cancer progression, including tumor growth, angiogenesis, and metastasis.
- Targeting matrix metalloproteases (MMPs) has shown limited success due to side effects, necessitating exploration of alternative protease targets.
- Cathepsin L (CatL), a lysosomal cysteine protease, is implicated in cancer development and metastasis, making it a promising therapeutic target.
Purpose of the Study:
- To identify potential inhibitors of Cathepsin L (CatL) using computational methods.
- To evaluate the feasibility of repurposing existing drugs for CatL inhibition in cancer therapy.
- To explore novel therapeutic strategies for cancer management by targeting CatL.
Main Methods:
- Integrated virtual screening of the DrugBank database against CatL.
- Molecular dynamics (MD) simulations to assess the stability of drug-CatL interactions.
- Analysis of docking profiles, binding scores, and specific interactions within the CatL binding pocket.
Main Results:
- Virtual screening identified Irinotecan and Nilotinib as potential CatL inhibitors based on favorable docking.
- Molecular dynamics simulations demonstrated stable interactions between Irinotecan, Nilotinib, and CatL over 300 ns.
- Both drugs exhibited robust binding, suggesting their potential as CatL inhibitors.
Conclusions:
- Irinotecan and Nilotinib show promise as repurposed drugs for targeting Cathepsin L in cancer treatment.
- The study validates the use of computational approaches for identifying novel cancer therapeutics.
- These findings provide a foundation for future experimental research into CatL-targeted cancer therapies.
