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利用机器学习模型评估药物发现与开发中的ADMET性质。

Leveraging machine learning models in evaluating ADMET properties for drug discovery and development.

作者信息

Venkataraman Magesh, Rao Gopi Chand, Madavareddi Jeevan Karthik, Maddi Srinivas Rao

机构信息

Department of Pharmacology, Acubiosys Private Limited, Hyderabad, Telangana, India.

出版信息

ADMET DMPK. 2025 Jun 7;13(3):2772. doi: 10.5599/admet.2772. eCollection 2025.


DOI:10.5599/admet.2772
PMID:40585410
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12205928/
Abstract

BACKGROUND AND PURPOSE: The evaluation of ADMET properties remains a critical bottleneck in drug discovery and development, contributing significantly to the high attrition rate of drug candidates. Traditional experimental approaches are often time-consuming, cost-intensive, and limited in scalability. This review aims to investigate how recent advances in machine learning (ML) models are revolutionizing ADMET prediction by enhancing accuracy, reducing experimental burden, and accelerating decision-making during early-stage drug development. EXPERIMENTAL APPROACH: This article systematically examines the current landscape of ML applications in ADMET prediction, including the types of algorithms employed, common molecular descriptors and datasets used, and model development workflows. It also explores public databases, model evaluation metrics, and regulatory considerations relevant to computational toxicology. Emphasis is placed on supervised and deep learning techniques, model validation strategies, and the challenges of data imbalance and model interpretability. KEY RESULTS: ML-based models have demonstrated significant promise in predicting key ADMET endpoints, outperforming some traditional quantitative structure - activity relationship (QSAR) models. These approaches provide rapid, cost-effective, and reproducible alternatives that integrate seamlessly with existing drug discovery pipelines. Case studies discussed in this review illustrate the successful deployment of ML models for solubility, permeability, metabolism, and toxicity predictions. CONCLUSION: Machine learning has emerged as a transformative tool in ADMET prediction, offering new opportunities for early risk assessment and compound prioritization. While challenges such as data quality, algorithm transparency, and regulatory acceptance persist, continued integration of ML with experimental pharmacology holds the potential to substantially improve drug development efficiency and reduce late-stage failures.

摘要

背景与目的:药物吸收、分布、代谢、排泄及毒性(ADMET)性质的评估仍是药物研发中的关键瓶颈,这在很大程度上导致了候选药物的高淘汰率。传统的实验方法往往耗时、成本高且可扩展性有限。本综述旨在研究机器学习(ML)模型的最新进展如何通过提高准确性、减轻实验负担以及在药物早期研发过程中加速决策,从而彻底改变ADMET预测。 实验方法:本文系统地审视了ML在ADMET预测中的应用现状,包括所采用的算法类型、常用的分子描述符和数据集,以及模型开发工作流程。还探讨了与计算毒理学相关的公共数据库、模型评估指标和监管考量。重点关注监督学习和深度学习技术、模型验证策略以及数据不平衡和模型可解释性的挑战。 关键结果:基于ML的模型在预测关键ADMET终点方面已显示出巨大潜力,优于一些传统的定量构效关系(QSAR)模型。这些方法提供了快速、经济高效且可重复的替代方案,能够与现有的药物发现流程无缝集成。本综述中讨论的案例研究说明了ML模型在溶解度、渗透性、代谢和毒性预测方面的成功应用。 结论:机器学习已成为ADMET预测中的变革性工具,为早期风险评估和化合物优先级排序提供了新机会。尽管数据质量、算法透明度和监管接受度等挑战依然存在,但ML与实验药理学的持续整合有潜力大幅提高药物研发效率并减少后期失败。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ac/12205928/deb5696af40b/ADMET-13-2772-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ac/12205928/a2cf318c06a2/ADMET-13-2772-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ac/12205928/03e0ae87df42/ADMET-13-2772-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ac/12205928/deb5696af40b/ADMET-13-2772-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ac/12205928/a2cf318c06a2/ADMET-13-2772-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ac/12205928/03e0ae87df42/ADMET-13-2772-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ac/12205928/deb5696af40b/ADMET-13-2772-g003.jpg

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本文引用的文献

[1]
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Environ Mol Mutagen. 2025

[2]
Machine learning based radiomics model to predict radiotherapy induced cardiotoxicity in breast cancer.

J Appl Clin Med Phys. 2025-4

[3]
ChemXTree: A Feature-Enhanced Graph Neural Network-Neural Decision Tree Framework for ADMET Prediction.

J Chem Inf Model. 2024-11-25

[4]
Comprehensive hepatotoxicity prediction: ensemble model integrating machine learning and deep learning.

Front Pharmacol. 2024-8-21

[5]
Artificial intelligence in antidiabetic drug discovery: The advances in QSAR and the prediction of α-glucosidase inhibitors.

Comput Struct Biotechnol J. 2024-7-6

[6]
Understanding predictions of drug profiles using explainable machine learning models.

BioData Min. 2024-8-1

[7]
Multi-Task ADME/PK prediction at industrial scale: leveraging large and diverse experimental datasets.

Mol Inform. 2024-10

[8]
KG-LIME: predicting individualized risk of adverse drug events for multiple sclerosis disease-modifying therapy.

J Am Med Inform Assoc. 2024-8-1

[9]
Predicting ADMET Properties from Molecule SMILE: A Bottom-Up Approach Using Attention-Based Graph Neural Networks.

Pharmaceutics. 2024-6-7

[10]
A Machine Learning Approach for Predicting Caco-2 Cell Permeability in Natural Products from the Biodiversity in Peru.

Pharmaceuticals (Basel). 2024-6-7

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