Fu Chen, Yu Lifeng, Miao Yuxi, Liu Xinli, Yu Zhaojin, Wei Minjie
Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang 110122, China.
Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, China Medical University, Shenyang 110122, China.
Acta Pharm Sin B. 2023 Feb;13(2):498-516. doi: 10.1016/j.apsb.2022.07.020. Epub 2022 Aug 3.
Peptide-drug conjugates (PDCs) are the next generation of targeted therapeutics drug after antibody-drug conjugates (ADCs), with the core benefits of enhanced cellular permeability and improved drug selectivity. Two drugs are now approved for market by US Food and Drug Administration (FDA), and in the last two years, the pharmaceutical companies have been developing PDCs as targeted therapeutic candidates for cancer, coronavirus disease 2019 (COVID-19), metabolic diseases, and so on. The therapeutic benefits of PDCs are significant, but poor stability, low bioactivity, long research and development time, and slow clinical development process as therapeutic agents of PDC, how can we design PDCs more effectively and what is the future direction of PDCs? This review summarises the components and functions of PDCs for therapeutic, from drug target screening and PDC design improvement strategies to clinical applications to improve the permeability, targeting, and stability of the various components of PDCs. This holds great promise for the future of PDCs, such as bicyclic peptide‒toxin coupling or supramolecular nanostructures for peptide-conjugated drugs. The mode of drug delivery is determined according to the PDC design and current clinical trials are summarised. The way is shown for future PDC development.
肽-药物偶联物（PDCs）是继抗体-药物偶联物（ADCs）之后的下一代靶向治疗药物，具有增强细胞通透性和提高药物选择性等核心优势。目前已有两种药物获得美国食品药品监督管理局（FDA）批准上市，在过去两年中，制药公司一直在研发将PDCs作为癌症、2019冠状病毒病（COVID-19）、代谢疾病等的靶向治疗候选药物。PDCs的治疗效果显著，但作为治疗药物，其稳定性差、生物活性低、研发时间长且临床开发进程缓慢，如何更有效地设计PDCs以及PDCs的未来发展方向是什么？本综述总结了用于治疗的PDCs的组成部分和功能，从药物靶点筛选、PDC设计改进策略到临床应用，以提高PDCs各组分的通透性、靶向性和稳定性。这为PDCs的未来发展带来了巨大希望，例如双环肽-毒素偶联或用于肽偶联药物的超分子纳米结构。根据PDC设计确定药物递送方式并总结了当前的临床试验。展示了未来PDC发展的方向。
