针对EGFR向的抗癌药物的药理学指导审查,将gefitinib作为参考药物
Meenu1, Khursheed Ahmad Sheikh1, M Shaquiquzzaman1
1Drug Design and Medicinal Chemistry Lab, Department of Pharmaceutical Chemistry, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, 110062, India.
本综述详细介绍了表皮生长因子受体 (EGFR) 抑制剂的关键药理特征,指导下一代药物的开发,以克服非小细胞肺癌 (NSCLC) 的耐药性. 它突出了结构性见解,以提高功效和选择性.
科学领域:
- 在瘤学瘤学.
- 药用化学 医学化学
- 结构生物学 结构生物学
背景情况:
- 表皮生长因子受体 (EGFR) 是非小细胞肺癌 (NSCLC) 的关键标.
- 现有的EGFR抑制剂面临的挑战是耐药性和特异性.
- 了解药进化对于下一代药物设计至关重要.
研究的目的:
- 为了探索 EGFR 抑制剂跨代的核心药理特征.
- 引导开发能够克服耐药性的先进EGFR抑制剂.
- 识别持久的结合动机和结构改进,以提高功效和选择性.
主要方法:
- 发表的药理学框架和结晶学数据的综合调查.
- 使用gefitinib支架和EGFR结构进行结构-活性关系分析 (PDB: 4WKQ).
- 集成分子对接,分子动力学模拟和验证的实验室分析.
主要成果:
- 确定了包括链定向键,疏水相互作用和pi堆叠在内的基本结合.
- 突出了改进,如共价核弹头和灵活的溶剂尾巴,用于突变选择性.
- 发现三醇添加剂增强了对T790M和C797S变体的亲和力,减少了目标外影响.
结论:
- 药解体模式揭示了逃避多药理学的趋势.
- 一个多功能药模板可以促进新的脚手架发明.
- 这种方法加速了对耐用的第三代和第四代EGFR抑制剂的优化.
更多相关视频
09:38Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
13:34A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds
Published on: April 6, 2016
相关概念视频
Targeted Cancer Therapies
There are several types of targeted therapies against...
Mitogens and the Cell Cycle
Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
