National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Research Center for Precision Medication of Chinese Medicine, FuRong Laboratory, Hunan University of Chinese Medicine, Changsha, PR China; Hubei Engineering Research Center of Traditional Chinese Medicine of South Hubei Province, School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning, PR China; Department of Hepatology, China Military Institute of Chinese Materia, The Fifth Medical Center of PLA General Hospital, Beijing, PR China.
National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Research Center for Precision Medication of Chinese Medicine, FuRong Laboratory, Hunan University of Chinese Medicine, Changsha, PR China; Hubei Engineering Research Center of Traditional Chinese Medicine of South Hubei Province, School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning, PR China.
Eur J Med Chem. 2024 Oct 5;276:116725. doi: 10.1016/j.ejmech.2024.116725. Epub 2024 Jul 30.
Drug development remains a critical focus within the global pharmaceutical industry. To date, more than 80 % of disease targets are considered difficult to target. The emergence of PROTAC technology has, to some extent, alleviated this challenge. Since introduction, PROTAC technology has evolved through the peptide E3 ligase ligand phase and the small molecule E3 ligase ligand phase. Currently, multiple PROTAC molecules are in the clinical research phase, showing promising potential for addressing drug resistance, disease recurrence, and intractable targets. Target deconvolution is a crucial step in the drug discovery and development process. Due to the exceptional targeting ability and specificity of PROTAC, it is widely used and promoted as an innovative technology for discovering new drug targets, leading to significant breakthroughs. The use of PROTAC probe requires only a catalytic dose and weak interaction with the target protein to achieve target degradation. Thus, it offers substantial advantages over traditional probes, particularly in identifying new targets that are low-abundance or difficult to target. This review provides a comprehensive overview of the advancements made by PROTAC technology in drug development and drug target discovery, while also systematically reviewing the workflow of PROTAC probe. With the ongoing development of PROTAC technology, PROTAC probe is poised to become a key research area in future drug target deconvolution.
药物研发仍然是全球制药行业的一个关键焦点。迄今为止，超过 80%的疾病靶点被认为难以靶向。PROTAC 技术的出现在一定程度上缓解了这一挑战。自问世以来，PROTAC 技术经历了肽 E3 连接酶配体阶段和小分子 E3 连接酶配体阶段的发展。目前，多种 PROTAC 分子正处于临床研究阶段，在解决耐药性、疾病复发和难治性靶点方面显示出巨大的潜力。靶标分解是药物发现和开发过程中的关键步骤。由于 PROTAC 具有出色的靶向能力和特异性，它被广泛应用和推广为发现新药物靶点的创新技术，带来了重大突破。PROTAC 探针的使用仅需催化剂量，并且与靶蛋白的弱相互作用即可实现靶标降解。因此，与传统探针相比，它具有显著的优势，尤其是在识别低丰度或难以靶向的新靶标方面。本综述全面概述了 PROTAC 技术在药物开发和药物靶标发现方面的进展，同时系统回顾了 PROTAC 探针的工作流程。随着 PROTAC 技术的不断发展，PROTAC 探针有望成为未来药物靶标分解的一个关键研究领域。
