均相抗体-药物通过选择性二硫桥接偶联

Q1 Pharmacology, Toxicology and Pharmaceutics

Drug Discovery Today: Technologies Pub Date : 2018-12-01 DOI:10.1016/j.ddtec.2018.09.004

Nafsika Forte, Vijay Chudasama, James R. Baker

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引用次数: 29

摘要

使用位点选择性标记方法构建的抗体-药物偶联物(adc)可能会主导下一代这些靶向治疗方法。为此，二硫桥接已成为一种领先的策略，因为它允许在不需要抗体工程的情况下生产高度均匀的adc。它包括用试剂靶向减少的链间二硫键，这些试剂重新连接所产生的半胱氨酸残基对，同时附着药物。本文综述了目前用于二硫桥接法合成adc的三种主要试剂;双砜类、下一代马来酰亚胺类和吡嗪二酮类，以及其他正在开发中的类。

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Homogeneous antibody-drug conjugates via site-selective disulfide bridging

Antibody-drug conjugates (ADCs) constructed using site-selective labelling methodologies are likely to dominate the next generation of these targeted therapeutics. To this end, disulfide bridging has emerged as a leading strategy as it allows the production of highly homogeneous ADCs without the need for antibody engineering. It consists of targeting reduced interchain disulfide bonds with reagents which reconnect the resultant pairs of cysteine residues, whilst simultaneously attaching drugs. The 3 main reagent classes which have been exemplified for the construction of ADCs by disulfide bridging will be discussed in this review; bissulfones, next generation maleimides and pyridazinediones, along with others in development.

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来源期刊

Drug Discovery Today: Technologies Pharmacology, Toxicology and Pharmaceutics-Drug Discovery

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期刊介绍： Discovery Today: Technologies compares different technological tools and techniques used from the discovery of new drug targets through to the launch of new medicines.