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Current Computer-Aided Drug Design


ISSN (Print): 1573-4099
ISSN (Online): 1875-6697

Research Article

Structural Insights into the Molecular Design of ROS1 Inhibitor for the Treatment of Non-Small Cell Lung Cancer (NSCLC)

Author(s): Ritu Adhikary, Ravina Khandelwal, Tajamul Hussain, Anuraj Nayarisseri* and Sanjeev K. Singh*

Volume 17, Issue 3, 2021

Published on: 04 May, 2020

Page: [387 - 401] Pages: 15

DOI: 10.2174/1573409916666200504105249

Price: $65


Background: Non-Small Cell Lung Cancer (NSCLC) alone is the leading cause of deaths worldwide. ROS1 is a receptor tyrosine kinase (RTK), eminently recognized as the stereotyped oncogenic driver. These RTKs trigger an array of physiological regulations via cellular signal transduction pathways, which are crucial for cancer development. This attributed ROS1 as an appealing and potential target towards the targeted cancer therapy. The present research aims to propound out an effective contemporary inhibitor for targeting ROS1 with a high affinity.

Methods: Molegro Virtual Docker (MVD) provided a flexible docking platform to find out the bestestablished drug as an inhibitor for targeting ROS1. A similarity search was accomplished against the PubChem database to acquire the corresponding inhibitor compounds regarding the Entrectinib (Pub- Chem ID: 25141092). These compounds were docked to procure the high-affinity inhibitor for the target protein via virtual screening. A comparative study between the control molecule (PubChem ID: 25141092)and the virtual screened compound(PubChem ID-25175866) was performed for the relative analysis of their salient features, which involved pharmacophore mapping, ADMET profiling, and BOILED-Egg plot.

Results: The virtual screened compound (PubChem ID-25175866) possesses the lowest rerank score (-126.623), and the comparative ADMET analysis also shows that it is a potential and effective inhibitor for ROS1 among the selected inhibitors.

Conclusion: The present study provided a scope for the ROS1 inhibitor as significant prevention for nonsmall cell lung cancer (NSCLC). It can be upheld for future studies as a promising support via in vivo studies.

Keywords: ROS1, Non-Small Cell Lung Cancer (NSCLC), molecular docking, virtual screening, ADMET, inhibitor.

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