TY - JOUR KW - 3Rs principle KW - animal studies KW - Artificial intelligence KW - deep learning KW - Digital Twins KW - generative adversarial networks KW - Machine Learning KW - organ-on-chip AU - Amit Gangwal AU - Antonio Lavecchia AB - Artificial intelligence (AI) is reshaping preclinical drug research offering innovative alternatives to traditional animal testing. Advanced techniques, including machine learning (ML), deep learning (DL), AI-powered digital twins (DTs), and AI-enhanced organ-on-a-chip (OoC) platforms, enable precise simulations of complex biological systems. AI plays a critical role in overcoming the limitations of DTs and OoC, improving their predictive power and scalability. These technologies facilitate early-stage, reliable evaluations of drug safety and efficacy, addressing ethical concerns, reducing costs, and accelerating drug development while adhering to the 3Rs principle (Replace, Reduce, Refine). By integrating AI with these advanced models, preclinical research can achieve greater accuracy and efficiency in drug discovery. This review examines the transformative impact of AI in preclinical research, highlighting its advancements, challenges, and the critical steps needed to establish AI as a cornerstone of ethical and efficient drug discovery. BT - Drug Discovery Today DA - 2025-05-01 DO - 10.1016/j.drudis.2025.104360 IS - 5 N2 - Artificial intelligence (AI) is reshaping preclinical drug research offering innovative alternatives to traditional animal testing. Advanced techniques, including machine learning (ML), deep learning (DL), AI-powered digital twins (DTs), and AI-enhanced organ-on-a-chip (OoC) platforms, enable precise simulations of complex biological systems. AI plays a critical role in overcoming the limitations of DTs and OoC, improving their predictive power and scalability. These technologies facilitate early-stage, reliable evaluations of drug safety and efficacy, addressing ethical concerns, reducing costs, and accelerating drug development while adhering to the 3Rs principle (Replace, Reduce, Refine). By integrating AI with these advanced models, preclinical research can achieve greater accuracy and efficiency in drug discovery. This review examines the transformative impact of AI in preclinical research, highlighting its advancements, challenges, and the critical steps needed to establish AI as a cornerstone of ethical and efficient drug discovery. PY - 2025 EP - 104360 ST - Artificial intelligence in preclinical research T2 - Drug Discovery Today TI - Artificial intelligence in preclinical research: enhancing digital twins and organ-on-chip to reduce animal testing UR - https://www.sciencedirect.com/science/article/pii/S135964462500073X VL - 30 Y2 - 2025-09-03 SN - 1359-6446 ER -