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FormulationBCS: A Machine Learning Platform Based on Diverse Molecular Representations for Biopharmaceutical Classification System (BCS) Class Prediction | |
Wu, Zheng1; Wang, Nannan1; Ye, Zhuyifan2; Xu, Huanle3; Chan, Ging1,4; Ouyang, Defang1,4 | |
2024-12-08 | |
Source Publication | Molecular Pharmaceutics |
ISSN | 1543-8384 |
Abstract | The Biopharmaceutics Classification System (BCS) has facilitated biowaivers and played a significant role in enhancing drug regulation and development efficiency. However, the productivity of measuring the key discriminative properties of BCS, solubility and permeability, still requires improvement, limiting high-throughput applications of BCS, which is essential for evaluating drug candidate developability and guiding formulation decisions in the early stages of drug development. In recent years, advancements in machine learning (ML) and molecular characterization have revealed the potential of quantitative structure-performance relationships (QSPR) for rapid and accurate in silico BCS classification. The present study aims to develop a web platform for high-throughput BCS classification based on high-performance ML models. Initially, four data sets of BCS-related molecular properties: log S, log P, log D, and log P were curated. Subsequently, 6 ML algorithms or deep learning frameworks were employed to construct models, with diverse molecular representations ranging from one-dimensional molecular fingerprints, descriptors, and molecular graphs to three-dimensional molecular spatial coordinates. By comparing different combinations of molecular representations and learning algorithms, LightGBM exhibited excellent performance in solubility prediction, with an R of 0.84; AttentiveFP outperformed others in permeability prediction, with R values of 0.96 and 0.76 for log P and log D, respectively; and XGBoost was the most accurate for log P prediction, with an R of 0.71. When externally validated on a marketed drug BCS category data set, the best-performing models achieved classification accuracies of over 77 and 73% for solubility and permeability, respectively. Finally, the well-trained models were embedded into the first ML-based BCS class prediction web platform (x f), enabling pharmaceutical scientists to quickly determine the BCS category of candidate drugs, which will aid in the high-throughput BCS assessment for candidate drugs during the preformulation stage, thereby promoting reduced risk and enhanced efficiency in drug development and regulation. |
Keyword | Bcs Prediction Machine Learning Artificial Intelligence Platform Preformulation Solubility Permeability |
DOI | 10.1021/acs.molpharmaceut.4c00946 |
URL | View the original |
Indexed By | SCIE |
Language | 英語English |
WOS Research Area | Research & Experimental Medicine ; Pharmacology & Pharmacy |
WOS Subject | Medicine, Research & Experimental ; Pharmacology & Pharmacy |
WOS ID | WOS:001372911300001 |
Publisher | AMER CHEMICAL SOC, 1155 16TH ST, NW, WASHINGTON, DC 20036 |
Scopus ID | 2-s2.0-85211457811 |
Fulltext Access | |
Citation statistics | |
Document Type | Journal article |
Collection | Faculty of Health Sciences Faculty of Science and Technology Institute of Chinese Medical Sciences THE STATE KEY LABORATORY OF QUALITY RESEARCH IN CHINESE MEDICINE (UNIVERSITY OF MACAU) DEPARTMENT OF PUBLIC HEALTH AND MEDICINAL ADMINISTRATION |
Corresponding Author | Ouyang, Defang |
Affiliation | 1.Institute of Chinese Medical Sciences (ICMS), State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, 999078, Macao 2.Faculty of Applied Sciences, Macao Polytechnic University, 999078, Macao 3.Faculty of Science and Technology, University of Macau, 999078, Macao 4.Department of Public Health and Medicinal Administration, Faculty of Health Sciences (FHS), University of Macau, 999078, Macao |
First Author Affilication | Institute of Chinese Medical Sciences |
Corresponding Author Affilication | Institute of Chinese Medical Sciences; Faculty of Health Sciences |
Recommended Citation GB/T 7714 | Wu, Zheng,Wang, Nannan,Ye, Zhuyifan,et al. FormulationBCS: A Machine Learning Platform Based on Diverse Molecular Representations for Biopharmaceutical Classification System (BCS) Class Prediction[J]. Molecular Pharmaceutics, 2024. |
APA | Wu, Zheng., Wang, Nannan., Ye, Zhuyifan., Xu, Huanle., Chan, Ging., & Ouyang, Defang (2024). FormulationBCS: A Machine Learning Platform Based on Diverse Molecular Representations for Biopharmaceutical Classification System (BCS) Class Prediction. Molecular Pharmaceutics. |
MLA | Wu, Zheng,et al."FormulationBCS: A Machine Learning Platform Based on Diverse Molecular Representations for Biopharmaceutical Classification System (BCS) Class Prediction".Molecular Pharmaceutics (2024). |
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