Accelerating Drug Discovery With High-Throughput Crystallographic Fragment Screening and Structural Enablement

被引：0

作者：

Fearon, Daren ^{[1
,2
]}

Powell, Ailsa ^{[1
,2
]}

Douangamath, Alice ^{[1
,2
]}

Dias, Alexandre ^{[1
,2
]}

Tomlinson, Charles W. E. ^{[1
,2
]}

Balcomb, Blake H. ^{[1
,2
]}

Aschenbrenner, Jasmin C. ^{[1
,2
]}

Aimon, Anthony ^{[1
,2
]}

Barker, Isabel A. ^{[1
,2
]}

Brandão-Neto, José ^{[1
,2
]}

Collins, Patrick ^{[1
,2
]}

Dunnett, Louise E. ^{[1
,2
]}

Fairhead, Michael ^{[3
]}

Gildea, Richard J. ^{[1
]}

Golding, Mathew ^{[1
,2
]}

Gorrie-Stone, Tyler ^{[1
,2
]}

Hathaway, Paul V. ^{[1
]}

Koekemoer, Lizbé ^{[3
]}

Krojer, Tobias ^{[3
]}

Lithgo, Ryan M. ^{[1
,2
]}

Maclean, Elizabeth M. ^{[3
]}

Marples, Peter G. ^{[1
,2
]}

Ni, Xiaomin ^{[3
]}

Skyner, Rachael ^{[1
,2
]}

Talon, Romain ^{[1
,2
]}

Thompson, Warren ^{[1
,2
]}

Wild, Conor F. ^{[1
,2
]}

Winokan, Max ^{[1
,2
]}

Wright, Nathan David ^{[3
]}

Winter, Graeme ^{[1
]}

Shotton, Elizabeth J. ^{[1
]}

von Delft, Frank ^{[1
,2
,3
,4
]}

机构：

[1] Diamond Light Source Ltd, Harwell Science and Innovation Campus, Oxfordshire, Didcot, United Kingdom

[2] Research Complex at Harwell, Harwell Science and Innovation Campus, Oxfordshire, Didcot, United Kingdom

[3] Centre for Medicines Discovery, University of Oxford, NDM Research Building, Oxfordshire, Oxford, United Kingdom

[4] Department of Biochemistry, University of Johannesburg, Johannesburg, South Africa

来源：

Applied Research | 2025年 / 4卷 / 01期

关键词：

Drug discovery;

D O I：

10.1002/appl.202400192

中图分类号：

学科分类号：

摘要：

Fragment-based drug discovery is a well-established method for the identification of chemical starting points for development into clinical candidates. Historically, crystallographic fragment screening was perceived to be low-throughput and time consuming. However, thanks to advances in synchrotron capabilities and the introduction of dedicated facilities, such as the XChem platform at Diamond Light Source, there have been substantial improvements in throughput and integration between sample preparation, data collection and hit identification. Herein we share our experiences of establishing a crystallographic fragment screening facility, our learnings from operating a user programme for ten years and our perspective on applying structural enablement to rapidly progress initial fragment hits to lead-like molecules. © 2024 The Author(s). Applied Research published by Wiley-VCH GmbH.

引用

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