Discovery of Cobimetinib as a novel A-FABP inhibitor using machine learning and molecular docking-based virtual screening

Abstract

The integrated virtual screening pipeline was constructed to identify potential inhibitors of A-FABP in the latest FDA-approved drug library, aiming to explore the existing drugs with proven safety profiles.

TCMBank: bridges between the largest herbal medicines, chemical ingredients, target proteins, and associated diseases with intelligence text mining

“…Gong et al 84 utilized multiple machine learning methods to screen TCM for the treatment of diabetes, ultimately selecting Hypecoum leptocarpum. Yang et al 85 utilized naïve Bayesian (NB) models and molecular docking to screen FDA-approved drugs for the treatment of metabolic diseases targeting the A-FABP target. He et al 86 used machine learning and graph neural network methods to screen TCM for the treatment of multiple vascular tumors, ultimately selecting Mulberry leaf and Ganoderma lucidum .…”

Discovery of novel SOS1 inhibitors using machine learning

“… 21 In another study, Yang et al employed a combined approach of ligand-based ML and structural-based molecular docking to screen the latest US Food and Drug Administration approved drug library (∼2600 compounds) for potential inhibitors of adipocyte fatty acid-binding protein, seeking to investigate current medications with established safety characteristics. 22 The results demonstrated the efficacy of the naïve Bayesian model in predicting potential inhibitors, leading to the discovery of cobimetinib, which was subsequently confirmed to inhibit A-FABP-activated JNK/C-jun phosphorylation in cellular assays. Other related research efforts are focused on the discovery of lead anti-cancer compounds such as lysine-specific histone demethylase 1, 23 and indoleamine 2,3-dioxygenase inhibitors.…”

The Effects of FABP4 on Cardiovascular Disease in the Aging Population

“…By combining machine learning and molecular docking on the approximately 2600 compounds in the FDA-approved drug library ( https://go.drugbank.com ), four different compounds (cobimetinib, larotrectinib, pantoprazole, and vildagliptin) were identified [ 88 ]. Cobimetinib, a mitogen-activated protein kinase (MEK)-specific small molecule inhibitor, is a drug used in melanoma (cancer) research and out of the four the most effective inhibitor of FABP4 [ 89 , 90 ].…”