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使用吡咯并苯二氮䓬类及相关共价结合DNA的相互作用分子作为抗体药物偶联物（ADC）的有效载荷：其作用机制与全身毒性有关吗？

Use of pyrrolobenzodiazepines and related covalent-binding DNA-interactive molecules as ADC payloads: Is mechanism related to systemic toxicity?

作者信息

Jackson Paul J M, Kay Syafiq, Pysz Ilona, Thurston David E

机构信息

Femtogenix Ltd., Biopark, Broadwater Road, Welwyn Garden City AL7 3AX, United Kingdom.

Femtogenix Ltd., Biopark, Broadwater Road, Welwyn Garden City AL7 3AX, United Kingdom; Institute for Pharmaceutical Science, King's College London, Faculty of Life Sciences and Medicine, Franklin Wilkins Building, London SE1 9NH, United Kingdom.

出版信息

Drug Discov Today Technol. 2018 Dec;30:71-83. doi: 10.1016/j.ddtec.2018.10.004. Epub 2018 Dec 6.

DOI:10.1016/j.ddtec.2018.10.004
PMID:30553523
Abstract

Antibody-drug conjugates (ADCs) consist of monoclonal antibodies (mAbs) or antibody fragments conjugated to biologically active molecules (usually highly cytotoxic small molecules) through chemical linkers. Although no ADCs containing covalent-binding DNA-interactive payloads have yet been approved (although two containing the DNA-cleaving payload calicheamicin have), of those in clinical trials systemic toxicities are beginning to emerge. This article discusses the observed toxicities in relation to the structures and mechanisms of action of payload type.

摘要

抗体药物偶联物（ADCs）由单克隆抗体（mAbs）或抗体片段组成，这些抗体通过化学连接子与生物活性分子（通常是高细胞毒性小分子）偶联。尽管尚未有含共价结合DNA相互作用有效载荷的ADC获批（不过有两种含DNA裂解有效载荷刺孢霉素的已获批），但在临床试验中的那些药物已开始出现全身毒性。本文讨论了观察到的毒性与有效载荷类型的结构和作用机制之间的关系。

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