Zeitschrift für Krebswissenschaft und -forschung
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Abstrakt

Exploring Molecular network and docking analysis of Osimertinib in cancer Cascade: Need for Drug Repurposing

Shweta A. More, Nikhil S. Sakle, Santosh N. Mokale*

Background: The network-target-based network pharmacology is a promising approach for the next generation of drug re- search and development for traditional as well as synthetic medicine. We report on the major in-depth molecular analysis of Osimertinib and provide new insight into molecular events involved in the progression of Non-small cell lung cancer.

Objective: Network pharmacology uses computational biology to develop our understanding of drug actions and to ad- vance drug discovery. Here we apply network pharmacology to generate testable hypothesis about multi-target mechanism of Osimertinib against Non-small-cell lung cancer (NSCLC).

Methods: We reconstructed drug-target pathways and network to predict the protein targets of Osimertinib and inter- actions between targets and the drug. Then we validated our prediction of five candidate targets (c-MET, EGFR, FGFR, VEGFR, ERR) by performing docking studies with Osimertinib.

Results: The results suggest that Osimertinib acts against NSCLC by regulating function of signaling proteins, including CREB, CDK-2, EGFR, TNF, BRPF-1, ErbB, PI3K/AKT, HIF-1, NFκB, CAMP, and HGF, which regulates the functions of various biological, molecular and cellular responses in NSCLC. Osimertinib is predicted to affect networks involved mainly in cancer viz., renal cell carcinoma, endometrial cancer, prostate cancer, and bladder cancer.

Conclusion: This approach of repurposing may be useful for multi-target drugs against complex diseases.