AI-Based Drug Discovery of TKIs Targeting L858R/T790M/C797S-Mutant EGFR in Non-small Cell Lung Cancer

Lung cancer has a high mortality rate, and non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Patients have been observed to acquire resistance against various anticancer agents used for NSCLC due to L858R (or Exon del19)/T790M/C797S-EGFR mutations. Therefore, next-generation drugs are being developed to overcome this problem of acquired resistance. The goal of this study was to use artificial intelligence (AI) to discover drug candidates that can overcome acquired resistance and reduce the limitations of the current drug discovery process, such as high costs and long durations of drug design and production. To generate ligands using AI, we collected data related to tyrosine kinase inhibitors (TKIs) from accessible libraries and used LSTM (Long short term memory) based transfer learning (TL) model. Through the simplified molecular-input line-entry system (SMILES) datasets of the generated ligands, we obtained drug-like ligands via parameter-filtering, cyclic skeleton (CSK) analysis, and virtual screening utilizing deep-learning method. Based on the results of this study, we are developing prospective EGFR TKIs for NSCLC that have overcome the limitations of existing third-generation drugs.