Amity Institute of Biotechnology, Amity University, Sector125, Noida, Uttar Pradesh, India.
Bioorg Chem. 2021 Jul;112:104946. doi: 10.1016/j.bioorg.2021.104946. Epub 2021 Apr 27.
Targeted delivery combined with controlled release of drugs has a crucial role in future of personalized medicine. The majority of cancer drugs are intended to interfere with one or more cellular events. Anticancer agents can also be toxic to healthy cells, as healthy cells may also need to proliferate and avoid apoptosis. The focus of this review covers the principles, advantages, drawbacks and summarize criteria that must be met for design of small molecule-drug conjugates (SMDCs) to achieve the desired therapeutic potency with minimal toxicity. SMDCs are composed of a targeting ligand, a releasable bridge, a spacer, and a therapeutic payload. We summarize the criteria for the effective design that influences the selection of tumor specific receptor and optimum elements in the design of SMDCs. We also discuss the criteria for selecting the optimal therapeutic drug payload, spacer and linker. The linker chemistries and cleavage strategies are also discussed. Finally, we review the folate receptor targeting SMDCs that are in preclinical development and in clinical trials.
靶向给药与药物控释在个性化医学的未来中具有关键作用。大多数癌症药物旨在干扰一个或多个细胞事件。抗癌药物也可能对健康细胞有毒，因为健康细胞也可能需要增殖并避免凋亡。本综述的重点涵盖了小分子药物偶联物（SMDC）设计的原则、优点、缺点，并总结了实现所需治疗效力和最小毒性的设计标准。SMDC 由靶向配体、可释放桥、间隔物和治疗有效载荷组成。我们总结了影响肿瘤特异性受体选择和 SMDC 设计中最佳元素的有效设计标准。我们还讨论了选择最佳治疗药物有效载荷、间隔物和连接子的标准。还讨论了连接化学和切割策略。最后，我们综述了处于临床前开发和临床试验阶段的叶酸受体靶向 SMDC。
