抗體偶聯(lián)藥物（ADC）是由單克隆抗體和細(xì)胞毒性有效載荷通過(guò)連接子偶聯(lián)而成，結(jié)合了單克隆抗體的高特異性靶向能力和細(xì)胞毒活性小分子高效殺傷作用的優(yōu)點(diǎn)，實(shí)現(xiàn)了對(duì)癌細(xì)胞的精準(zhǔn)高效清除，已成為抗癌藥物研發(fā)的熱點(diǎn)之一。自2000年美國(guó)食品藥品監(jiān)督管理局（FDA）批準(zhǔn)第一個(gè)ADC藥物吉妥珠單抗（Mylotarg）以來(lái)，迄今全球已有14個(gè)ADC藥物獲批上市。這類(lèi)新型的抗癌藥物正引領(lǐng)癌癥靶向治療的新時(shí)代?；贏DC藥物的構(gòu)建核心和抗腫瘤作用機(jī)制，對(duì)ADC藥物的體內(nèi)外代謝的研究進(jìn)展進(jìn)行綜述，以期從代謝角度為ADC藥物的設(shè)計(jì)、開(kāi)發(fā)、臨床前藥理、毒理及后續(xù)研究提供參考。

Antibody-drug conjugates (ADC) are formed by coupling monoclonal antibodies and cytotoxic payloads through linkers. ADC drugs combine the advantages of high specific targeting ability of monoclonal antibodies and efficient killing effect of small cytotoxic molecules to achieve accurate and efficient removal of cancer cells, and have become one of the hot spots in the research and development of anticancer drugs. Since the food and Drug Administration (FDA) approved the first ADC drug Mylotarg (gemtuzumab ozogamicin) in 2000, so far, 14 ADC drugs have been approved for marketing in the world. This new anticancer drug is leading a new era of cancer targeted therapy. Based on the core construction and anti-tumor mechanism of ADC drugs, the research progress of in vitro and in vivo metabolism of ADC drugs is reviewed, in order to provide more references for the design, development, preclinical pharmacology / toxicology and follow-up research of ADC drugs from the perspective of metabolism.

R979.1;R965.3

江蘇省創(chuàng)新能力建設(shè)計(jì)劃科技公共服務(wù)平臺(tái)項(xiàng)目(BM2021002)