Abstract:
Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. Despite the availability of various therapeutic options, NSCLC remains a major health concern due to its aggressive nature and high mutation rate. Therefore, HER3 has been selected as a target protein along with EGFR due to its limited tyrosine kinase activity and its ability to activate the PI3/AKT pathway, which is responsible for therapy failure. In this study, a BioSolveIT suite was utilized to identify potent inhibitors of EGFR and HER3. The process involved screening databases to construct a compound library consisting of 903 synthetic compounds (602 for EGFR and 301 for HER3), followed by pharmacophore modeling. The best docked poses of the compounds with the druggable binding site of their respective proteins were selected based on the pharmacophore design using SeeSAR version 12.1.0. Subsequently, preclinical analysis was conducted using the online server SwissADME, and potent inhibitors were identified. Compound 4k and 4m demonstrated the most potent inhibition of EGFR, while 7x effectively inhibited the binding site of HER3. The binding energies of 4k, 4m, and 7x were determined to be -7.7, -6.3, and -5.7 kcal/mol, respectively. Collectively, these compounds exhibited favorable interactions with the most druggable binding sites of their respective target proteins. Finally, in silico preclinical testing by SwissADME confirmed the non-toxic nature of compounds 4k, 4m, and 7x, providing a promising treatment option for chemoresistant NSCLC. It's important to note that further experimental validation, including in vitro and in vivo studies, is necessary to confirm the efficacy and safety of these identified compounds before considering them for clinical use.
Page(s):
384-384
DOI:
DOI not available
Published:
Journal: Abstract Book on International Conference on Food and Applied Sciences (ICFAS-23) 3-5 August 23, Volume: 0, Issue: 0, Year: 2023