School of Pharmacy, Lanzhou University, Lanzhou, 730000, Gansu, China.
Beijing Zhongyan Tongrentang Medicine R&D Co., Ltd, Beijing, 100079, China.
Sci Rep. 2024 Oct 7;14(1):23297. doi: 10.1038/s41598-024-74243-5.
Drug repositioning is gaining attention as a method for developing new drugs due to its low cost, short cycle time, and high success rate. One important approach is to explore new uses for already marketed drugs. In this study, we utilized the strategy of drug repositioning, focusing on the Dan-Lou tablet. We predicted the efficacy of Dan-Lou tablet against non-small cell lung cancer based on gene expression similarity and verified it by in vitro experiments. Next, we performed further analysis and validation using network pharmacology, molecular docking and molecular dynamics. Based on the results, it was concluded that Dan-Lou tablet mainly acted through nine compounds, Quercetin, Luteolin, Scoparone, Isorhamnetin, Eugenol, Genistein, Coumestrol, Hederagenin, Succinic Acid, and mainly targeted CCL2, FEN1, TPI1, RMI2 by six pathways. This discovery not only provides a new idea for the development of Dan-Lou tablet but also provides useful predictive information for clinical treatment. The method we adopted has great development prospects as a way to predict the efficacy of new drugs and their main mechanisms of action, and it has a positive impact on the research and development of new drugs using drug repositioning and the modernization of traditional Chinese medicine.
药物重定位作为一种开发新药的方法,由于其成本低、周期短、成功率高而受到关注。一种重要的方法是探索已经上市的药物的新用途。在这项研究中,我们利用药物重定位策略,重点研究丹鹿片。我们基于基因表达相似性预测丹鹿片对非小细胞肺癌的疗效,并通过体外实验进行了验证。接下来,我们使用网络药理学、分子对接和分子动力学进行了进一步的分析和验证。基于这些结果,我们得出结论,丹鹿片主要通过 9 种化合物,槲皮素、木樨草素、獐牙菜苦苷、异鼠李素、丁香酚、染料木素、大豆苷元、猪去氧胆酸、琥珀酸起作用,主要通过 6 条途径靶向 CCL2、FEN1、TPI1、RMI2。这一发现不仅为丹鹿片的开发提供了新的思路,也为临床治疗提供了有用的预测信息。我们采用的方法作为预测新药疗效及其主要作用机制的方法具有广阔的发展前景,对药物重定位和中药现代化的新药研发具有积极的影响。