Optimizing the Cardiotoxicity Profile of Osimertinib via Scaffold Hopping: An Integrated Cheminformatics and Molecular Modeling Approach

Journal of Computational Biophysics and Chemistry 2026

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Authors: Narendra R. Nagpure, Vaibhav Kadam, Bhatu R. Patil, Sampath Chinnam, Chandrakant Gawli, Iqrar Ahmad, Harun Patel
DOI: 10.1142/s2737416526500754
Cited by: 1

Abstract

Osimertinib, a third-generation covalent epidermal growth factor receptor (EGFR) inhibitor widely used to treat EGFR T790M-positive non-small cell lung cancer (NSCLC), is limited by dose-dependent cardiotoxicity driven by human ether-à-go-go-related gene (hERG) channel inhibition. To design safer analogues, we applied an integrated computational workflow combining ADMET filtering, covalent docking, molecular dynamics, and quantum-chemical analysis. Using ADMETopt and admetSAR 2.0, a scaffold-hopping campaign generated 390 analogs, of these 161 compounds exhibited substantially reduced predicted hERG inhibition (

Fields of Study & Subjects

Lung Cancer Treatments and Mutations Computational Drug Discovery Methods Quinazolinone synthesis and applications

Publication details

Journal / source
Journal of Computational Biophysics and Chemistry
Publisher
World Scientific Pub Co Pte Ltd
Pages
1–32
Publication date
10 April 2026
Language
EN