中药柴胡、生姜、甘草方具有显着的抗癌作用，但其活性成分和抑制机制尚不清楚。本工作通过网络药理学鉴定了核心有效成分槲皮素及其信号转导子和转录激活子3（Stat3）受体。槲皮素是一种低毒、非致癌的黄酮类化合物，具有抗氧化、抗炎和抗癌活性，广泛分布于食用植物中。 Stat3可以与特定的DNA反应元件结合，并作为转录因子促进一些侵袭/迁移相关靶基因的翻译，被认为是潜在的抗癌靶点。这里，我们使用分子对接和分子动力学（MD）模拟来探索Stat3对槲皮素的分子识别。结果表明，槲皮素通过阻碍 Stat3 二聚化、部分破坏 DNA 构象来损害 DNA 转录效率。具体来说，当配体占据酶的 SH2 空腔时，空间排斥不利于磷酸激酶结合。它间接阻止 Y705 的磷酸化和 Stat3 二聚体的形成。当抑制剂与DT1005位点结合时，明显缩短了DNA和DBD之间的距离，增强了它们的结合能力，从而降低了转录所需的自由度。该工作不仅提供了Stat3与槲皮素的结合模式，也有助于此类抗癌抑制剂的优化和设计。版权所有：©2024 Jiang et al.这是一篇根据知识共享署名许可条款分发的开放获取文章，允许在任何媒体上不受限制地使用、分发和复制，前提是注明原始作者和来源。

The traditional Chinese medicine (TCM) bupleurum-ginger-licorice formula presents significant anti-cancer effects, but its active ingredients and inhibitory mechanism remain unclear. In this work, the core effective ingredient quercetin and its signal transducer and activator of transcription 3 (Stat3) receptor both were identified by network pharmacology. Quercetin is a low-toxicity, non-carcinogenic flavonoid with antioxidant, anti-inflammatory and anticancer activities, which is widely distributed in edible plants. Stat3 can bind to specific DNA response elements and serves as a transcription factor to promote the translation of some invasion/migration-related target genes, considered as a potential anticancer target. Here, molecular docking and molecular dynamics (MD) simulation both were used to explore molecular recognition of quercetin with Stat3. The results show that quercetin impairs DNA transcription efficiency by hindering Stat3 dimerization, partially destroying DNA conformation. Specifically, when the ligand occupies the SH2 cavity of the enzyme, spatial rejection is not conductive to phosphokinase binding. It indirectly prevents the phosphorylation of Y705 and the formation of Stat3 dimer. When the inhibitor binds to the DT1005 position, it obviously shortens the distance between DNA and DBD, enhances their binding capacity, and thereby reduces the degree of freedom required for transcription. This work not only provides the binding modes between Stat3 and quercetin, but also contributes to the optimization and design of such anti-cancer inhibitors.Copyright: © 2024 Jiang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.