Department of Chemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
Department of Organic Chemistry, Faculty of Sciences, University of Málaga, 29071 Málaga, Spain.
Mar Drugs. 2022 Jul 30;20(8):494. doi: 10.3390/md20080494.
Antibody-drug conjugates (ADCs) are an important class of therapeutics for the treatment of cancer. Structurally, an ADC comprises an antibody, which serves as the delivery system, a payload drug that is a potent cytotoxin that kills cancer cells, and a chemical linker that connects the payload with the antibody. Unlike conventional chemotherapy methods, an ADC couples the selective targeting and pharmacokinetic characteristics related to the antibody with the potent cytotoxicity of the payload. This results in high specificity and potency by reducing off-target toxicities in patients by limiting the exposure of healthy tissues to the cytotoxic drug. As a consequence of these outstanding features, significant research efforts have been devoted to the design, synthesis, and development of ADCs, and several ADCs have been approved for clinical use. The ADC field not only relies upon biology and biochemistry (antibody) but also upon organic chemistry (linker and payload). In the latter, total synthesis of natural and designed cytotoxic compounds, together with the development of novel synthetic strategies, have been key aspects of the consecution of clinical ADCs. In the case of payloads from marine origin, impressive structural architectures and biological properties are observed, thus making them prime targets for chemical synthesis and the development of ADCs. In this review, we explore the molecular and biological diversity of ADCs, with particular emphasis on those containing marine cytotoxic drugs as the payload.
抗体药物偶联物（ADCs）是治疗癌症的一类重要治疗药物。从结构上看，ADC 由抗体组成，抗体作为输送系统，有效载荷药物是一种有效的细胞毒素，可以杀死癌细胞，而化学连接子将有效载荷与抗体连接起来。与传统的化疗方法不同，ADC 将抗体的选择性靶向和药代动力学特性与有效载荷的强大细胞毒性结合在一起。这通过将健康组织暴露于细胞毒性药物的程度限制在最低水平，从而提高了特异性和效力，降低了患者的脱靶毒性。由于这些突出的特点，人们投入了大量的研究努力来设计、合成和开发 ADC，并且已经有几种 ADC 被批准用于临床使用。ADC 领域不仅依赖于生物学和生物化学（抗体），还依赖于有机化学（连接子和有效载荷）。在后一种情况下，天然和设计的细胞毒性化合物的全合成，以及新的合成策略的发展，一直是临床 ADC 成功的关键方面。在海洋来源的有效载荷的情况下，观察到令人印象深刻的结构架构和生物学特性，因此它们是化学合成和 ADC 开发的主要目标。在这篇综述中，我们探讨了 ADC 的分子和生物学多样性，特别强调了那些含有海洋细胞毒性药物作为有效载荷的 ADC。
