ROS1 kinase inhibition reimagined: identifying repurposed drug via virtual screening and molecular dynamics simulations for cancer therapeutics
Mohammed Alrouji, Sabina Yasmin, Fahad A Alhumaydhi, Sharaf E. Sharaf, Moyad Shahwan, Anas Shamsi
TL;DR
This study identifies Midostaurin and Alectinib as potential repurposed drugs for ROS1 kinase inhibition in cancer treatment using virtual screening and molecular dynamics simulations.
Contribution
The study proposes a novel framework for drug repurposing targeting ROS1 kinase using virtual screening and MD simulations.
Findings
Midostaurin and Alectinib showed favorable binding profiles with ROS1 kinase domain.
Molecular dynamics simulations confirmed the stability of Midostaurin and Alectinib with ROS1.
The study provides a rational framework for repurposing drugs targeting ROS1 for cancer therapy.
Abstract
Precision medicine has revolutionized modern cancer therapeutic management by targeting specific molecular aberrations responsible for the onset and progression of tumorigenesis. ROS proto-oncogene 1 (ROS1) is a receptor tyrosine kinase (RTK) that can induce tumorigenesis through various signaling pathways, such as cell proliferation, survival, migration, and metastasis. It has emerged as a promising therapeutic target in various cancer types. However, there is very limited availability of specific ROS1 inhibitors for therapeutic purposes. Exploring repurposed drugs for rapid and effective treatment is a useful approach. In this study, we utilized an integrated approach of virtual screening and molecular dynamics (MD) simulations of repurposing existing drugs for ROS1 kinase inhibition. Using a curated library of 3648 FDA-approved drugs, virtual screening identified drugs capable of…
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Taxonomy
TopicsComputational Drug Discovery Methods · Cancer therapeutics and mechanisms · Protein Structure and Dynamics