使用吡咯苯二氮卓类药物和相关的共价结合dna相互作用分子作为ADC有效载荷:机制是否与全身毒性有关?

Q1 Pharmacology, Toxicology and Pharmaceutics

Drug Discovery Today: Technologies Pub Date : 2018-12-01 DOI:10.1016/j.ddtec.2018.10.004

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

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引用次数: 16

摘要

抗体-药物偶联物(adc)由单克隆抗体(mab)或抗体片段通过化学连接物偶联到生物活性分子(通常是高细胞毒性小分子)组成。虽然目前还没有含有共价结合dna相互作用有效载荷的adc被批准(虽然有两种含有dna切割有效载荷的calicheamicin)，但在临床试验中，这些adc开始出现全身毒性。本文讨论了所观察到的与有效载荷类型的结构和作用机制有关的毒性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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

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.

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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.