This study investigates the application of a deep learning (DL) model, specifically a message-passing neural network (MPNN) implemented through Chemprop, to predict the persistence, bioaccumulation, and toxicity (PBT) characteristics of compounds, with a focus on pharmaceuticals. We employed a clustering strategy to provide a fair assessment of the model performances. By applying the generated model to a set of pharmaceutically relevant molecules, we aim to highlight potential PBT chemicals and extract PBT-relevant substructures. These substructures can serve as structural flags, alerting drug designers to potential environmental issues from the earliest stages of the drug discovery process. Incorporating these findings into pharmaceutical development workflows is expected to drive significant advancements in creating more environmentally friendly drug candidates while preserving their therapeutic efficacy.

Evangelista, D., Nelson, E., Skyner, R., Tehan, B., Bernetti, M., Roberti, M., et al. (2025). Application of Deep Learning to Predict the Persistence, Bioaccumulation, and Toxicity of Pharmaceuticals. JOURNAL OF CHEMICAL INFORMATION AND MODELING, 65(7), 3248-3261 [10.1021/acs.jcim.4c02293].

Application of Deep Learning to Predict the Persistence, Bioaccumulation, and Toxicity of Pharmaceuticals

Evangelista, Dominga;Bernetti, Mattia;Roberti, Marinella;Bolognesi, Maria Laura
;
Bottegoni, Giovanni
2025

Abstract

This study investigates the application of a deep learning (DL) model, specifically a message-passing neural network (MPNN) implemented through Chemprop, to predict the persistence, bioaccumulation, and toxicity (PBT) characteristics of compounds, with a focus on pharmaceuticals. We employed a clustering strategy to provide a fair assessment of the model performances. By applying the generated model to a set of pharmaceutically relevant molecules, we aim to highlight potential PBT chemicals and extract PBT-relevant substructures. These substructures can serve as structural flags, alerting drug designers to potential environmental issues from the earliest stages of the drug discovery process. Incorporating these findings into pharmaceutical development workflows is expected to drive significant advancements in creating more environmentally friendly drug candidates while preserving their therapeutic efficacy.
2025
Evangelista, D., Nelson, E., Skyner, R., Tehan, B., Bernetti, M., Roberti, M., et al. (2025). Application of Deep Learning to Predict the Persistence, Bioaccumulation, and Toxicity of Pharmaceuticals. JOURNAL OF CHEMICAL INFORMATION AND MODELING, 65(7), 3248-3261 [10.1021/acs.jcim.4c02293].
Evangelista, Dominga; Nelson, Elliot; Skyner, Rachael; Tehan, Ben; Bernetti, Mattia; Roberti, Marinella; Bolognesi, Maria Laura; Bottegoni, Giovanni...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/1036460
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