SpotXplorer (Live)

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.

Compounds

• 96 fragments
• Varying concentrations in d6-DMSO

SMILES: Click to download the SpotXplorer plate map

For follow-ups, please contact: György M Keserű

PUBLICATION to cite:

"Exploring protein hotspots by optimized fragment pharmacophores" Bajusz, D. et al. Nature Communications volume 12, Article number: 3201 (2021) 

ACKNOWLEDGEMENT text to use: 

SpotXplorer library was provided by the Keserű lab at RCNS, Hungary (http://medchem.ttk.hu).