非小细胞肺癌（NSCLC）仍然是全球癌症相关死亡的主要原因。目前的治疗通常不能完全满足疗效和生活质量预期。传统中医（TCM），特别是益气散结方，显示出了希望，但缺乏清晰的机制认识。本研究通过研究益气散结方在 NSCLC 中的治疗效果和潜在机制来弥补这一空白。我们利用网络药理学，通过中药系统药理学 (TCMSP) 数据库识别益气散结方潜在的 NSCLC 药物靶点。选择具有良好口服生物利用度和药物相似性评分的化合物。使用 AutoDock Vina 以及来自蛋白质数据库和 PubChem 的结构数据进行分子对接。使用 Desmond 分子动力学系统进行分子动力学 (MD) 模拟，使用 OPLS4 力场分析长达 500 纳秒的相互作用。使用 SwissADME 和 ADMETlab 2.0 执行 ADMET 预测，评估药代动力学特性。使用网络药理学工具，我们对蛋白质-蛋白质相互作用进行了相互作用基因/蛋白质检索搜索工具 (STRING) 分析，京都基因和基因组百科全书 (KEGG)用于途径富集，以及用于功能富集的基因本体 (GO)，识别受热门化合物联苯双酯、xambioona 和常春藤素影响的关键信号传导途径和生物过程。 STRING 分析表明靶标之间存在显着的连通性，这表明细胞周期调节和生长因子信号传导途径之间存在显着的相互作用，如我们的 KEGG 结果中所述。 GO 分析强调了它们参与细胞周期控制、细胞凋亡和药物反应等关键生物过程。分子对接模拟量化了已识别化合物与其靶标（CCND1、CDK4 和 EGFR）的结合效率，这些靶标是基于高对接分数选择的，表明对 NSCLC 抑制至关重要的强大潜在相互作用。随后的 MD 模拟验证了这些复合物的稳定性，支持它们作为治疗干预的潜力。此外，新发现的 ADH1B 作为靶点强调了其在 NSCLC 治疗中的前瞻性意义，并通过我们的综合生物信息学方法进一步扩展。我们的研究证明了整合网络药理学和计算生物学来阐明益气散结方在 NSCLC 治疗中的机制的潜力。所鉴定的化合物可能会导致新的靶向治疗，特别是对于靶标过度表达的患者。 ADH1B 作为治疗靶点的发现为 NSCLC 治疗策略增添了新的维度。需要进一步的体外和体内研究来证实这些计算结果并将这些化合物推进临床试验。2024 转化癌症研究。版权所有。

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related deaths globally. Current treatments often do not fully meet efficacy and quality of life expectations. Traditional Chinese medicine (TCM), particularly the Yiqi Sanjie formula, shows promise but lacks clear mechanistic understanding. This study addresses this gap by investigating the therapeutic effects and underlying mechanisms of Yiqi Sanjie formula in NSCLC.We utilized network pharmacology to identify potential NSCLC drug targets of the Yiqi Sanjie formula via the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Compounds with favorable oral bioavailability and drug-likeness scores were selected. Molecular docking was conducted using AutoDock Vina with structural data from the Protein Data Bank and PubChem. Molecular dynamics (MD) simulations were performed with Desmond Molecular Dynamics System, analyzing interactions up to 500 nanoseconds using the OPLS4 force field. ADMET predictions were executed using SwissADME and ADMETlab 2.0, assessing pharmacokinetic properties.Using network pharmacology tools, we performed Search Tool for the Retrieval of Interaction Genes/Proteins (STRING) analysis for protein-protein interaction, Kyoto Encyclopedia of Genes and Genomes (KEGG) for pathway enrichment, and gene ontology (GO) for functional enrichment, identifying crucial signaling pathways and biological processes influenced by the hit compounds bifendate, xambioona, and hederagenin. STRING analysis indicated substantial connectivity among the targets, suggesting significant interactions within the cell cycle regulation and growth factor signaling pathways as outlined in our KEGG results. The GO analysis highlighted their involvement in critical biological processes such as cell cycle control, apoptosis, and drug response. Molecular docking simulations quantified the binding efficiencies of the identified compounds with their targets-CCND1, CDK4, and EGFR-selected based on high docking scores that suggest strong potential interactions crucial for NSCLC inhibition. Subsequent MD simulations validated the stability of these complexes, supporting their potential as therapeutic interventions. Additionally, the novel identification of ADH1B as a target underscores its prospective significance in NSCLC therapy, further expanded by our comprehensive bioinformatics approach.Our research demonstrates the potential of integrating network pharmacology and computational biology to elucidate the mechanisms of the Yiqi Sanjie formula in NSCLC treatment. The identified compounds could lead to novel targeted therapies, especially for patients with overexpressed targets. The discovery of ADH1B as a therapeutic target adds a new dimension to NSCLC treatment strategies. Further studies, both in vitro and in vivo, are needed to confirm these computational findings and advance these compounds towards clinical trials.2024 Translational Cancer Research. All rights reserved.