药物缀合物是从肿瘤定位载体中获得的，该载体通过连接体与细胞毒性剂连接，旨在将剧毒有效负载直接传递到目标癌细胞。这些药物偶联物包括抗体-药物偶联物（ADC）、肽-药物偶联物（PDC）、小分子-药物偶联物（SMDC）、核酸适体-药物偶联物（ApDC）和病毒样药物偶联物（VDC），在临床上显示出巨大的治疗价值。药物偶联物由靶向载体、连接体和有效负载组成。有效负载是关键的治疗组件。源自天然产物的细胞毒性分子及其衍生物通常用于缀合物的有效负载部分。理想的有效负载应具有足够的毒性、稳定性、偶联位点以及在特定条件下释放杀死肿瘤细胞的能力。微管蛋白抑制剂、DNA损伤剂和RNA抑制剂是常见的细胞毒性分子。在这些缀合物中，根据其作用机制、构象关系和新衍生物的发现对天然来源的细胞毒性分子进行了总结。本文还提到了一些有可能成为有效载荷的细胞毒性分子。它还总结了近年来开发的最新技术和新型结合物，以克服 ADC、PDC、SMDC、ApDC 和 VDC 的缺点。此外，本文还总结了过去五年来对这些细胞毒性分子的缀合物进行的临床试验。它为设计和开发更安全、更高效的缀合物提供了参考。版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。

Drug conjugates are obtained from tumor-located vectors connected to cytotoxic agents via linkers, which are designed to deliver hyper-toxic payloads directly to targeted cancer cells. These drug conjugates include antibody-drug conjugates (ADCs), peptide-drug conjugates (PDCs), small molecule-drug conjugates (SMDCs), nucleic acid aptamer-drug conjugates (ApDCs), and virus-like drug conjugate (VDCs), which show great therapeutic value in the clinic. Drug conjugates consist of a targeting carrier, a linker, and a payload. Payloads are key therapy components. Cytotoxic molecules and their derivatives derived from natural products are commonly used in the payload portion of conjugates. The ideal payload should have sufficient toxicity, stability, coupling sites, and the ability to be released under specific conditions to kill tumor cells. Microtubule protein inhibitors, DNA damage agents, and RNA inhibitors are common cytotoxic molecules. Among these conjugates, cytotoxic molecules of natural origin are summarized based on their mechanism of action, conformational relationships, and the discovery of new derivatives. This paper also mentions some cytotoxic molecules that have the potential to be payloads. It also summarizes the latest technologies and novel conjugates developed in recent years to overcome the shortcomings of ADCs, PDCs, SMDCs, ApDCs, and VDCs. In addition, this paper summarizes the clinical trials conducted on conjugates of these cytotoxic molecules over the last five years. It provides a reference for designing and developing safer and more efficient conjugates.Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.