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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 Kumar Singh   Pages 1 - 15 ( 15 )

Abstract:


BACKGROUND: The Non-Small Cell Lung Cancer (NSCLC) alone is responsible for the sovereignty of demises worldwide related to the other cancers.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 the cancer development. This attributed ROS1 as an appealing and potential target towards the targeted cancer therapy. The aim of the present research is 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 best established drug as an inhibitor for targeting ROS1. A similarity search was accomplished against the PubChem database to acquire the corresponding inhibitor compounds with reference to the Entrectinib (PubChem 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 ID25175866) 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) possess 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 a significant prevention for the non-small cell lung cancer (NSCLC). It can be upheld for the future studies as a promising support via in vivo studies.

Keywords:

ROS1, Non-Small Cell Lung Cancer (NSCLC), Molecular Docking, Virtual Screening, ADMET

Affiliation:

In silico Research Laboratory, Eminent Biosciences, Mahalakshmi Nagar, Indore – 452010, Madhya Pradesh, In silico Research Laboratory, Eminent Biosciences, Mahalakshmi Nagar, Indore – 452010, Madhya Pradesh, Bioinformatics Research Laboratory, LeGene Biosciences Pvt Ltd., Indore - 452010, Madhya Pradesh, In silico Research Laboratory, Eminent Biosciences, Mahalakshmi Nagar, Indore – 452010, Madhya Pradesh, Computer Aided Drug Designing and Molecular Modeling Lab, Department of Bioinformatics, Alagappa University, Karaikudi-630 003, Tamil Nadu



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