Establishment of extensive artificial intelligence models for kinase inhibitor prediction: Identification of novel PDGFRB inhibitors

Identifying hit compounds is an important step in drug development. Unfortunately, this process continues to be a challenging task. Several machine learning models have been generated to aid in simplifying and improving the prediction of candidate compounds. Models tuned for predicting kinase inhibitors have been established. However, an effective model can be limited by the size of the chosen training dataset. In this study, we tested several machine learning models to predict potential kinase inhibitors. A dataset was curated from a number of publicly available repositories. This resulted in a comprehensive dataset covering more than half of the human kinome. More than 2,000 kinase models were established using different model approaches. The performances of the models were compared, and the Keras-MLP model was determined to be the best performing model. The model was then used to screen a chemical library for potential inhibitors targeting platelet-derived growth factor receptor-β (PDGFRB). Several PDGFRB candidates were selected, and in vitro assays confirmed four compounds with PDGFRB inhibitory activity and IC₅₀ values in the nanomolar range. These results show the effectiveness of machine learning models trained on the reported dataset. This report would aid in the establishment of machine learning models as well as in the discovery of novel kinase inhibitors.