Drug Repurposing for Colorectal Cancer: In Silico Identification of Pazopanib and Brequinar as Potential Therapeutics Targeting Oncogenic Pathways

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Pratiksha Bhoi, Shouryan Patil, Shraddha Ranpise, and Preeti Mate (Department of Bioinformatics, Dr. D. Y. Patil Arts, Commerce & Science College, Pimpri, Pune, Maharashtra)

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths globally, with its incidence projected to double by 2035, especially in developing regions. Challenges in treatment arise from disease complexity, drug resistance, and the high costs of traditional drug discovery. This study explores drug repurposing as a faster, cost-effective alternative by targeting key oncogenic pathways: EGFR/MAPK, Wnt/β-catenin, and PI3K/AKT. In silico screening of FDA-approved drugs identified Pazopanib and Brequinar as promising candidates. Molecular docking revealed strong binding affinities for PI3K (-11.72 & -9.62 kcal/mol) and MEK (-10.94 & -8.77 kcal/mol), surpassing Regorafenib. Molecular dynamics simulations further confirmed Brequinar’s stability with PI3K and KRAS, while ADMET analysis showed favorable pharmacokinetics despite high plasma protein binding. These findings suggest Pazopanib and Brequinar hold potential as effective CRC therapies, meriting further experimental validation.