Drug Safety and Metabolism, Innovative Medicines and Early Development, AstraZeneca, Cambridge CB4 0WG, United Kingdom; email:
TissUse, Berlin 13347, Germany.
Annu Rev Pharmacol Toxicol. 2018 Jan 6;58:65-82. doi: 10.1146/annurev-pharmtox-010617-052722. Epub 2017 Oct 13.
Enhancing the early detection of new therapies that are likely to carry a safety liability in the context of the intended patient population would provide a major advance in drug discovery. Microphysiological systems (MPS) technology offers an opportunity to support enhanced preclinical to clinical translation through the generation of higher-quality preclinical physiological data. In this review, we highlight this technological opportunity by focusing on key target organs associated with drug safety and metabolism. By focusing on MPS models that have been developed for these organs, alongside other relevant in vitro models, we review the current state of the art and the challenges that still need to be overcome to ensure application of this technology in enhancing drug discovery.
提高对新疗法的早期检测能力，这些新疗法在目标患者人群中可能存在安全隐患，这将是药物发现领域的重大进展。微生理系统 (MPS) 技术提供了一个机会，可以通过生成更高质量的临床前生理数据来支持增强的临床前到临床转化。在这篇综述中，我们通过关注与药物安全性和代谢相关的关键靶器官，突出了这一技术机遇。通过关注针对这些器官开发的 MPS 模型以及其他相关的体外模型，我们回顾了当前的技术现状和仍然需要克服的挑战，以确保该技术在增强药物发现方面的应用。
