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

•More than 250 high throughput screens on a wide variety of targets have been completed by academic groups, small biotech, non-profits, and large pharma on a shared collection of half a million compounds.•An effective mechanism was set up for sharing proprietary screening compounds with full enablem...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Drug discovery today 2024-03, Vol.29 (3), p.103886-103886, Article 103886
Hauptverfasser: 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.
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:•More than 250 high throughput screens on a wide variety of targets have been completed by academic groups, small biotech, non-profits, and large pharma on a shared collection of half a million compounds.•An effective mechanism was set up for sharing proprietary screening compounds with full enablement of intellectual property creation.•Screening hits from the European Lead Factory have led to multiple active compound optimization programs at participating academic and industry organizations, and two companies have been created on the basis of hits from the ELF.•Analysis of the screening results indicate that compound promiscuity is correlated with lipophilicity and anti-correlated with three-dimensionality of compounds.•There is no indication of the existence of dark chemical matter in this collection, as we continuously observed previously inactive compounds to be active in new screens. 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.
ISSN:1359-6446
1878-5832
DOI:10.1016/j.drudis.2024.103886