TY  - JOUR
T1  - Multitask Deep Learning for CYP Inhibition, Inactivation, and Metabolic Soft-Spot Prediction
A1  - Nikolai Ivanov
A1  - Sergey Volkov
A1  - Elena Morozova
JF  - Pharmacophore
JO  - Pharmacophore
SN  - 2229-5402
Y1  - 2026
VL  - 17
IS  - 2
DO  - 10.51847/7FS6HA9tSy
SP  - 23
EP  - 33
N2  - CYP enzymes dominate drug clearance, and early recognition of inhibition, inactivation, and metabolic soft spots is central to modern drug design. A unified computational view of these liabilities could help prioritize safer chemical series before costly downstream testing. Existing models often treat reversible inhibition, time-dependent inactivation, and site-of-metabolism prediction as separate tasks. This separation can obscure the shared chemical determinants that drive binding, bioactivation, and metabolic transformation. This article describes a multitask deep learning model that jointly predicts CYP reversible inhibition, time-dependent inactivation, and metabolic soft-spot location from molecular structure. The objective is to use a shared molecular representation to support more consistent and data-efficient metabolic profiling. The proposed model uses a graph neural network backbone shared across three prediction heads. These heads conceptually support isoform-specific inhibition prediction, TDI risk prediction, and atom-level soft-spot localization within the same molecular framework. Conceptually, the model would be expected to improve consistency across related metabolic endpoints compared with isolated single-task systems. It could also connect molecule-level liability predictions with atom-level explanations that guide medicinal chemistry interpretation. A unified metabolic profiling model could streamline CYP liability assessment in early discovery. By combining inhibition, inactivation, and soft-spot prediction, such a model could provide a comprehensive and interpretable metabolic hazard panel from a single molecular input.
UR  - https://pharmacophorejournal.com/article/multitask-deep-learning-for-cyp-inhibition-inactivation-and-metabolic-soft-spot-prediction-pvkvhprejgykxpp
ER  -