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欧洲先导化合物工厂:十年公私合作药物发现项目的成果

The European Lead Factory: Results from a decade of collaborative, public-private, drug discovery programs.

作者信息

van Vlijmen Herman, Pannifer Andrew D, Cochrane Phil, Basting Daniel, Li Volkhart M, Engkvist Ola, Ortholand Jean-Yves, Wagener Markus, Duffy James, Finsinger Dirk, Davis Jeremy, van Helden Steven P, de Vlieger Jon S B

机构信息

Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium.

Biocity Scotland, Bo'ness Road, Newhouse ML1 5SH, UK.

出版信息

Drug Discov Today. 2024 Mar;29(3):103886. doi: 10.1016/j.drudis.2024.103886. Epub 2024 Jan 18.

Abstract

The European Lead Factory (ELF) is a consortium of universities and small and medium-sized enterprises (SMEs) dedicated to drug discovery, and the pharmaceutical industry. This unprecedented consortium provides high-throughput screening, triage, and hit validation, including to non-consortium members. The ELF library was created through a novel compound-sharing model between nine pharmaceutical companies and expanded through library synthesis by chemistry-specialized SMEs. The library has been screened against ∼270 different targets and 15 phenotypic assays, and hits have been developed to form the basis of patents and spin-off companies. Here, we review the outcome of screening campaigns of the ELF, including the performance and physicochemical properties of the library, identification of possible frequent hitter compounds, and the effectiveness of the compound-sharing model.

摘要

欧洲先导化合物工厂(ELF)是一个由致力于药物研发的大学以及中小企业(SME)和制药行业组成的联盟。这个史无前例的联盟提供高通量筛选、分类和活性验证服务,甚至面向非联盟成员。ELF文库是通过9家制药公司之间新颖的化合物共享模式创建的,并通过化学专业的中小企业进行文库合成得以扩充。该文库已针对约270个不同靶点和15种表型分析进行了筛选,并且已开发出的活性化合物构成了专利和衍生公司的基础。在此,我们回顾了ELF筛选活动的成果,包括文库的性能和物理化学性质、可能的频繁活性化合物的鉴定以及化合物共享模式的有效性。

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