Small molecule-drug conjugates: A novel strategy for cancer-targeted treatment
Small molecule-drug conjugates: A novel strategy for cancer-targeted treatment
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小分子药物偶联物：癌症靶向治疗的新策略
DOI：
10.1016/j.ejmech.2018.12.035
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发表时间：
2019
影响因子：
6.7
通讯作者：
Miao Zhenyuan
中科院分区：
文献类型：
--
作者：
Zhuang Chunlin;Guan Xianghong;Ma Hao;Cong Hui;Zhang Wannian;Miao Zhenyuan
靶向治疗已成为精准医学提高肿瘤治疗水平的有效策略。选择性的提高在现代肿瘤学中一直很受欢迎，因为在传统的癌症化疗中副作用减少。抗体-药物结合物(ADC)的使用是一种强有力的靶向治疗策略，它利用抗体选择性地将一种有效的细胞毒性化合物输送到肿瘤细胞，从而提高化疗药物的治疗效果。三种ADC产品(曲妥珠单抗恩坦辛、布妥昔单抗维多丁和inotuzumab ozogamicin)已经上市，几种化合物正在进行临床试验。与ADCs相比，小分子药物结合物(SMDC)为靶向给药提供了一种新的、更不成熟的视角。然而，SMDCs有几个优点：1)非免疫原性，2)更易于合成，3)较低的分子量，这赋予了良好的细胞在实体瘤中渗透的高潜力。因此，SMDC可能是一种很有前途的替代方案，具有与ADC相似的疗效。在本文中，我们重点介绍SMDC设计中的药物化学方面。将讨论以配体、连接物和小分子有效载荷为目标的SMDC。还将包括将SMDC用作治疗剂和SMDC其他应用的成功案例。
Targeted therapy has become an effective strategy of precision medicine for improving cancer treatment. Selectivity improvement is always popular in modern oncology because of decreased side effects in conventional cancer chemotherapy. The use of antibody-drug conjugates (ADC), a robust strategy for targeted therapy, applies antibodies to selectively deliver a potent cytotoxic compound to tumor cells and thus improve the therapeutic efficacy of the chemotherapeutic agents. Three ADC products (trastuzumab emtansine, brentuximab vedotin and inotuzumab ozogamicin) are already on the market, and several compounds are in clinical trials. Compared with ADCs, small molecule-drug conjugates (SMDCs) provide a new, less established perspective for targeted delivery. Nevertheless, SMDCs have several strengths: they have 1) a non-immunogenic nature, 2) much more manageable synthesis, 3) lower molecular weights, which confer a high potential for good cell penetration in solid tumors. SMDCs might therefore be a promising alternative with similar efficacy to ADCs. In this article, we highlight the medicinal chemistry aspects of SMDC design. SMDC targeting ligands, linkers and small-molecule payloads will be discussed. Successful cases of SMDCs used as therapeutic agents and other applications of SMDC will also be included.