Duocarmycins are a class of DNA minor-groove-binding alkylating molecules. For the past decade, various duocarmycin analogues have been used as payloads in the development of antibody–drug conjugates (ADCs). Currently, more than 15 duocarmycin-based ADCs have been studied preclinically, and some of them such as SYD985 have been granted Fast-Track Designation status. Nevertheless, progress in duocarmycin-based ADCs also faces challenges, with setbacks including the termination of BMS-936561/MDX-1203. In this review, we discuss issues associated with the efficacy, pharmacokinetic profile, and toxicological activity of these biotherapeutics. Furthermore, we summarize the latest advances in duocarmycin-based ADCs that have different target specificities and linker chemistries. Evidence from preclinical and clinical studies has indicated that duocarmycin-based ADCs are promising biotherapeutics for oncological application in the future.

多卡霉素是一类 DNA 小沟结合烷基化分子。在过去的十年中，各种多卡霉素类似物已被用作开发抗体-药物偶联物 (ADC) 的有效载荷。目前，已有超过 15 个基于多卡霉素的 ADC 进行了临床前研究，其中一些如 SYD985 已获得快速通道指定状态。尽管如此，基于多卡霉素的 ADC 的进展也面临挑战，其中包括终止 BMS-936561/MDX-1203。在这篇综述中，我们讨论了与这些生物治疗药物的疗效、药代动力学特征和毒理学活性相关的问题。此外，我们总结了基于多卡霉素的 ADC 的最新进展，这些 ADC 具有不同的靶标特异性和接头化学性质。