Use of pyrrolobenzodiazepines and related covalent-binding DNA-interactive molecules as ADC payloads: Is mechanism related to systemic toxicity?
Use of pyrrolobenzodiazepines and related covalent-binding DNA-interactive molecules as ADC payloads: Is mechanism related to systemic toxicity?
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DOI：
10.1016/j.ddtec.2018.10.004
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发表时间：
2018-12-01
期刊：
影响因子：
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通讯作者：
Thurston, David E
中科院分区：
文献类型：
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作者：
Jackson, Paul J M;Kay, Syafiq;Thurston, David E
抗体-药物偶联物（ADC）由通过化学接头与生物活性分子（通常是高细胞毒性小分子）偶联的单克隆抗体（mAb）或抗体片段组成。尽管尚未批准含有共价结合DNA相互作用有效载荷的ADC（尽管两种含有DNA切割有效载荷的加利车霉素已被批准），但在临床试验中，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的关系。
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.