Challenges and Opportunities to Develop Enediyne Natural Products as Payloads for Antibody-Drug Conjugates.
Challenges and Opportunities to Develop Enediyne Natural Products as Payloads for Antibody-Drug Conjugates.
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DOI：
10.1093/abt/tbab001
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发表时间：
2021-01
影响因子：
--
通讯作者：
Rader C
中科院分区：
文献类型：
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作者：
Adhikari A;Shen B;Rader C
Calicheamicin是抗体-药物偶联物（adc） gemtuzumab ozogamicin （Mylotarg®）和inotuzumab ozogamicin （Besponsa®）的有效载荷，属于烯二炔类天然产物。自1985年neocarzinostatin发色团的分离和结构鉴定以来，enediynes在癌症化疗中作为DNA损伤剂的价值引起了人们的广泛关注。由于它们对癌症细胞和健康细胞都具有非歧视性的细胞毒性，因此临床利用烯二炔天然产物依赖于偶联到适当的递送系统，如抗体。在这里，我们回顾了enediynes作为第一代和下一代adc有效载荷的现状。
Calicheamicin, the payload of the antibody-drug-conjugates (ADCs) gemtuzumab ozogamicin (Mylotarg®) and inotuzumab ozogamicin (Besponsa®), belongs to the class of enediyne natural products. Since the isolation and structural determination of the neocarzinostatin chromophore in 1985, the enediynes have attracted considerable attention for their value as DNA damaging agents in cancer chemotherapy. Due to their non-discriminatory cytotoxicity towards both cancer and healthy cells, the clinical utilization of enediyne natural products relies on conjugation to an appropriate delivery system, such as an antibody. Here, we review the current landscape of enediynes as payloads of first-generation and next-generation ADCs.