Fragment-based screening is now well-established as a powerful approach to early drug ("lead") discovery.
This is a library of small heterocyclic electrophiles. These are essentially covalent MiniFrags, comprising five and six-membered nitrogen-containing heterocycles with electron-withdrawing character that activates small electrophilic substituents (halogens, ethynyl, vinyl and nitrile groups). X-ray screening of ultra-low-molecular-weight ligands (MiniFrags) was successfully applied to identify viable chemical starting points for a variety of drug targets. The covalent version goes further and might provide powerful starting points for covalent ligand discovery, coupling the advantages of the MiniFrags with the fixed binding modes due to the minimal size warheads of 1 or 2 heavy atoms. The library contains not only small electrophilic heterocycles, but also their N-quaternized analogues with increased reactivity.
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 fragment reactivity, specificity, biophysical, biochemical and virtual screening and follow-up options. Please note that a siginificant part of the library is not available at commercial vendors, however, but we can provide refills upon request.
SMILES: click to download the CovHetFrags plate map
For follow-ups, please contact: György M Keserű
PUBLICATIONS to cite:
Covalent fragment libraries in drug discovery
Drug Discovery Today, 2020, 25, 983-996.
MedChemComm, 2019, 10, 263-267
ACKNOWLEDGEMENT text to use:
CovHetFrag library was provided by the Keserű lab at RCNS, Hungary (http://medchem.ttk.hu).
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