Ministry of Education Key Laboratory of Molecular and Cellular Biology, Hebei Anti-Tumor Molecular Target Technology Innovation Center, Hebei Research Center of the Basic Discipline of Cell Biology, College of Life Science, Hebei Normal University, Shijiazhuang 050024, P.R. China.
School of Chemical Technology, Shijiazhuang University, Shijiazhuang 050035, P.R. China.
J Med Chem. 2024 Jul 25;67(14):11469-11487. doi: 10.1021/acs.jmedchem.4c00106. Epub 2024 Jul 9.
Antibody-drug conjugates (ADCs) comprise antibodies, cytotoxic payloads, and linkers, which can integrate the advantages of antibodies and small molecule drugs to achieve targeted cancer treatment. However, ADCs also have some shortcomings, such as non-negligible drug resistance, a low therapeutic index, and payload-related toxicity. Many studies have focused on changing the composition of ADCs, and some have even further extended the concept and types of targeted conjugated drugs by replacing the targeted antibodies in ADCs with peptides, revolutionarily introducing peptide-drug conjugates (PDCs). This Perspective summarizes the current research status of ADCs and PDCs and highlights the structural innovations of ADC components. In particular, PDCs are regarded as the next generation of potential targeted drugs after ADCs, and the current challenges of PDCs are analyzed. Our aim is to offer fresh insights for the efficient design and expedited development of innovative targeted conjugated drugs.
抗体药物偶联物（ADCs）由抗体、细胞毒性有效载荷和连接子组成，可整合抗体和小分子药物的优势，实现靶向癌症治疗。然而，ADC 也存在一些缺点，如不可忽视的耐药性、治疗指数低和有效载荷相关毒性。许多研究都集中在改变 ADC 的组成上，有些研究甚至通过用肽替代 ADC 中的靶向抗体，进一步扩展了靶向偶联药物的概念和类型，革命性地引入了肽药物偶联物（PDCs）。本观点总结了 ADC 和 PDC 的当前研究现状，并强调了 ADC 成分的结构创新。特别是，PDCs 被认为是 ADC 之后的下一代潜在靶向药物，分析了 PDC 目前面临的挑战。我们的目的是为高效设计和加速开发创新靶向偶联药物提供新的见解。
