Fragment-based screening is now well-established as a powerful approach to early drug ("lead") discovery.
Combining the use of pharmacophores, the most general concept of representing drug-target interactions with the theory of protein hotspots we developed a novel design protocol for fragment libraries. The SpotXplorer approach compiles small fragment libraries that maximize the coverage of X-ray confirmed binding pharmacophores at the most preferred hotspots. The efficiency of this approach is demonstrated with a library of 96 fragment-sized compounds that has been validated on popular target classes and emerging drug targets. Screening against a set of GPCRs and proteases retrieved compounds containing an average of 70% of known pharmacophores for these targets. In addition, SpotXplorer screening identified confirmed hits against recently established challenging targets such as the histone methyltransferase SETD2 with no non-nucleoside ligand and the main protease (3CLPro) and the NSP3 macrodomain of SARS-CoV-2.
Before using the library please contact György M Keserű and his group at RCNS Hungary (http://medchem.ttk.hu). Depending on the target and its availability we can provide further infomation on fragmentspecificity, biophysical, biochemical and virtual screening and follow-up options.
SMILES: Click to download the SpotXplorer plate map
For follow-ups, please contact: György M Keserű
PUBLICATION to cite:
ACKNOWLEDGEMENT text to use:
SpotXplorer library was provided by the Keserű lab at RCNS, Hungary (http://medchem.ttk.hu).
Diamond Light Source is the UK's national synchrotron science facility, located at the Harwell Science and Innovation Campus in Oxfordshire.
Copyright © 2020 Diamond Light Source
Diamond Light Source Ltd
Harwell Science & Innovation Campus
Diamond Light Source® and the Diamond logo are registered trademarks of Diamond Light Source Ltd
Registered in England and Wales at Diamond House, Harwell Science and Innovation Campus, Didcot, Oxfordshire, OX11 0DE, United Kingdom. Company number: 4375679. VAT number: 287 461 957. Economic Operators Registration and Identification (EORI) number: GB287461957003.