Snail protein inhibition by drug repositioning for recurrent breast cancer: an in-silico study

Abstract

Objective: Snail is a transcription factor that promotes epithelial-mesenchymal transition (EMT) and facilitates tumor progression and metastasis in breast cancer. Therefore, it is a promising target for the development of anticancer agents. The objective of this study was to identify FDA-approved drugs that can be repurposed as Snail inhibitors. Materials and Methods: Using a virtual screening strategy, three molecules were selected among 1615 (Stivarga, Paritaprevir and Sorafenib). Molecular docking and molecular dynamics simulation were performed to examine Snail-drugs interactions. Results: Our docking analysis identified Stivarga and Sorafenib, two antineoplastic drugs, as potential repositioning drugs to treat recurrent breast cancer due to their low free binding energy values. Additional molecular dynamics simulations of the Snail-drug systems revealed that Sorafenib was the most stable, lasting from 30 to 120 ns and forming 2-4 hydrogen bonds. Conclusions: The antineoplastic drugs Stivarga and Sorafenib have better affinity and inhibition of Snail and could be a simple drug therapy for recurrent breast cancer.

Keywords

• snail
• breast cancer
• drug repositioning
• molecular docking
• md simulations