周梦圆, 赵骞, 卢琼, 陈诗懿, 谭倩倩, 谭睿. 干细胞模式分子靶向药物筛选模型的构建及应用J. 药学学报, 2025, 60(9): 2807-2817. DOI: 10.16438/j.0513-4870.2024-1282
引用本文: 周梦圆, 赵骞, 卢琼, 陈诗懿, 谭倩倩, 谭睿. 干细胞模式分子靶向药物筛选模型的构建及应用J. 药学学报, 2025, 60(9): 2807-2817. DOI: 10.16438/j.0513-4870.2024-1282
ZHOU Meng-yuan, ZHAO Qian, LU Qiong, CHEN Shi-yi, TAN Qian-qian, TAN Rui. Establishment and application of stem cell model molecular targeted drug screening modelJ. Acta Pharmaceutica Sinica, 2025, 60(9): 2807-2817. DOI: 10.16438/j.0513-4870.2024-1282
Citation: ZHOU Meng-yuan, ZHAO Qian, LU Qiong, CHEN Shi-yi, TAN Qian-qian, TAN Rui. Establishment and application of stem cell model molecular targeted drug screening modelJ. Acta Pharmaceutica Sinica, 2025, 60(9): 2807-2817. DOI: 10.16438/j.0513-4870.2024-1282

干细胞模式分子靶向药物筛选模型的构建及应用

Establishment and application of stem cell model molecular targeted drug screening model

  • 摘要: 神经性疾病、心血管疾病与肺部疾病一直是人类健康的主要威胁, 如何直观、高效、快速地筛选出具有治疗效果的药物是当下生物医学领域亟需攻克的关键科学问题。本研究针对3类疾病的病理特征, 克隆了神经生长因子、血管再生修复相关因子与肺炎相关因子等关键基因启动子并连接用于定量的报告基因。最终构建了基于干细胞分化体系的分子靶向药物筛选模型, 通过应用已知的通路激活剂对该模型进行功能验证。此模型不仅具备化合物药效预测的普适性特征, 且可针对中药及复方成分复杂的特性, 实现时效关系与量效关系的动态解析, 有效揭示其药效物质基础, 为后续临床用药的质量控制提供重要技术支撑。在保持传统筛选方法优势的同时, 突破了现有技术的局限性。最后, 本研究讨论了此药物筛选模型的技术特点, 并对其在药物研发领域的应用前景进行了前瞻性探讨。本研究所有动物福利和实验过程获得西南交通大学医学伦理委员会批准批准编号: SWJTU-2403-NSFC(026)。

     

    Abstract: Neurological diseases, cardiovascular diseases, and pulmonary diseases have always been major threats to human health. How to intuitively, efficiently, and rapidly screen out drugs with therapeutic effects is a key scientific issue in the field of biomedicine that urgently needs to be addressed. In this study, aiming at the pathological characteristics of these three types of diseases, key gene promoters such as those of nerve growth factor, vascular regeneration and repair factors and pneumonia factors were cloned and linked to reporter genes for quantification. Finally, a molecularly targeted drug screening model based on the stem cell differentiation system was constructed, and its function was verified by applying known pathway activators. This model not only has the universal characteristic of predicting the efficacy of compounds, but also can achieve dynamic analysis of the relationship between time and efficacy as well as the relationship between dosage and efficacy in view of the complex characteristics of traditional Chinese medicines and their compound ingredients, effectively revealing the material basis of their efficacy and providing important technical support for the quality control of subsequent clinical medications. While maintaining the advantages of traditional screening methods, this model breaks through the limitations of existing technologies. Finally, we discuss the technical characteristics of existing drug screening models and conduct a prospective discussion on the application prospects of this model in the field of drug research and development. The animal welfare and experimental procedures of the work were approved by the Medical Ethics Committee of Southwest Jiaotong University approval No. SWJTU-2403-NSFC(026).

     

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