从碎片到后续行动:通过使用EU-OPENSCREEN资源实现快速扩张
Laila S Benz1,2, Jan Wollenhaupt1, Aigars Jirgensons3
1Macromolecular Crystallography, Helmholtz-Zentrum Berlin Albert-Einstein-Str. 15 12489 Berlin Germany manfred.weiss@helmholtz-berlin.de.
RSC medicinal chemistry
|October 24, 2025
概括
从最初的片段查中开发出强效的候选药物是具有挑战性的. 这项研究展示了一种快速的方法,用于识别使用晶体学碎片查对内皮亚素和寨卡蛋白酶的后续化合物.
科学领域:
- 生物化学 生物化学
- 药物发现 药物发现 药物发现
- 结构生物学 结构生物学
背景情况:
- 碎片查对于确定药物开发的起点至关重要.
- 提前将初始碎片击中强效结合剂是一个重要的瓶.
- 复合开发的可访问途径对于项目成功至关重要.
研究的目的:
- 介绍两个结晶学碎片选活动.
- 展示一种快速识别后续化合物的方法.
- 验证欧盟-OPENSCREEN框架,以加速药物发现.
主要方法:
- 来自欧洲碎片选图书馆 (EFSL) 的96种化合物的晶体碎片选.
- 对内皮亚素和NS2B-NS3寨卡蛋白酶进行查.
- 来自欧洲化学生物学图书馆的测试相关化合物,用于后续结合剂.
主要成果:
- 对内皮亚素的成功率为31%,对NS2B-NS3寨卡蛋白酶的成功率为18%.
- 在一轮测试中,为每个目标确定两个后续结合剂.
- 欧盟-OPENSCREEN欧洲研究基础设施联盟 (ERIC) 方法的成功验证.
结论:
- 结晶学碎片选对于识别初始命中是有效的.
- 欧盟-OPENSCREEN框架有助于快速识别后续化合物.
- 这种综合方法加速了药物开发的早期阶段.
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