针对EML4-ALK融合蛋白相分离的药物研究与应用
Drug Research and Therapeutic Applications Targeting Phase Separation of the EML4-ALK Fusion Protein
王欣怡 1石碧1
作者信息
- 1. 湖南大学生物学院，湖南长沙，410082
- 折叠
摘要
EML4?ALK融合蛋白在非小细胞肺癌中具有重要致癌作用，其相分离特性可能成为新的药物干预靶点。本研究建立了HeLa?Trex稳转株，利用诱导表达系统和高内涵显微成像，对FDA批准药物库进行初筛。通过对3000余种化合物进行初步筛查，并定量分析细胞内液滴数量，筛选出对EML4-ALK液滴形成具有明显影响的候选药物。随后对初筛获得的候选药物进行进一步复筛，并结合显微观察对其作用效果进行确认。最终鉴定出5种潜在干预分子，为后续药理学研究及靶向治疗策略的探索提供了实验依据。
Abstract
The EML4-ALK fusion protein plays an important oncogenic role in non-small cell lung cancer, and its phase separation property may represent a novel therapeutic target. In this study, a stable HeLa-Trex cell line was established, and an inducible expression system combined with high-content imaging was used to perform a primary screen of an FDA-approved drug library. More than 3,000 compounds were initially screened, and intracellular droplet numbers were quantitatively analyzed to identify candidate compounds that had obvious effects on EML4-ALK droplet formation. The selected candidate compounds were then subjected to further rescreening, and their inhibitory effects were confirmed by microscopic observation. Ultimately, five potential small-molecule modulators were identified, providing an experimental basis for subsequent pharmacological studies and the exploration of targeted therapeutic strategies.关键词
EML4?ALK/相分离/非小细胞肺癌/药物筛选/高内涵显微Key words
EML4?ALK/phase separation/non?small cell lung cancer/drug screening/high-content imaging引用本文复制引用
王欣怡,石碧.针对EML4-ALK融合蛋白相分离的药物研究与应用[EB/OL].(2026-04-13)[2026-04-15].http://www.paper.edu.cn/releasepaper/content/202604-101.学科分类
生物科学研究方法、生物科学研究技术/细胞生物学/分子生物学
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