| 陈怡庆,曹中艳,徐元清,王玉霞.化学通报,2026,89(5):615-619. |
| 以死神之吻，赐生命以吻———三氧化二砷从毒物到靶向药物的转化之路 |
| With a Kiss from Death, Life is Kissed: The Transformation of Arsenic Trioxide from Poison to Targeted Therapy |
| 投稿时间：2025-11-27 修订日期：2026-03-03 |
| DOI： |
| 中文关键词: 三氧化二砷 急性早幼粒细胞白血病 药物开发 靶向治疗 以毒攻毒 |
| 英文关键词:Arsenic trioxide Acute promyelocytic leukemia (APL) Drug development Targeted therapy Like cures like |
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| 中文摘要: |
| 三氧化二砷（As2O3，砒霜）从传统毒物到现代靶向药物的转化，是药物化学史上的经典案例。20世纪70年代，中国科学家张亭栋等人运用成分分离与循证医学方法，从民间复方中锁定并验证了三氧化二砷对急性早幼粒细胞白血病（APL）的单一疗效。后续机制研究表明，三氧化二砷能靶向诱导PML-RARα融合蛋白降解，并通过线粒体途径触发癌细胞凋亡。在此基础上，其与全反式维甲酸（ATRA）联合形成的“上海方案”，通过诱导分化与诱导凋亡的协同作用，将APL从致死率最高的急性白血病转变为首种可被基本治愈的成人白血病。本文系统回顾了三氧化二砷从毒物到药物的转化历程、分子机制及其临床价值，并探讨其在新型制剂开发、适应症拓展等方向的最新研究进展。这一案例不仅诠释了“以毒攻毒”思想的现代科学内涵，也为基于天然产物的靶向药物研发提供了方法论启示。 |
| 英文摘要: |
| The transformation of arsenic trioxide (As2O3) from a traditional poison to a modern targeted drug represents a classic case in the history of medicinal chemistry. In the 1970s, Chinese scientist Zhang Tingdong and his colleagues, using component separation and evidence-based medicine, identified arsenic trioxide from a traditional compound recipe and validated its specific efficacy against acute promyelocytic leukemia (APL). Subsequent mechanistic studies revealed that arsenic trioxide targets and induces the degradation of the PML-RARα fusion protein and triggers cancer cell apoptosis through the mitochondrial pathway. Building on this, its combination with all-trans retinoic acid (ATRA), known as the "Shanghai Protocol," leverages the synergistic effects of inducing differentiation and apoptosis, transforming APL from a highly fatal acute leukemia into the first curable adult leukemia. This review systematically outlines the transformation of arsenic trioxide from poison to medicine, its molecular mechanisms, and clinical value, while also discussing the latest research advances in new formulations and expanded indications. This case not only exemplifies the modern scientific understanding of the concept of "Like cures like" but also provides methodological insights for the development of targeted drugs based on natural products. |
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