Another showcase story of the quality of Edelris’ SP3-rich Keymical Fragments™, used in fragment-based lead discovery. These remarkable results were obtained in collaboration with researchers from Merck KGA, EMD Serono, and Proteros Biostructures.
Fragment-based screening enabled the discovery of chemical diverse fragment hits with millimolar binding affinities to the peptidyl-prolyl isomerase Cyclophilin D (CypD). Merging and linking 3D-rich fragment hits from CypD co-crystal structures (KD=mM range) and a reference small molecule inhibitor (KD=230nM), followed by additional SAR-optimization improved extensively the in vitro affinities (1.2×10^6), as exemplified below.
This study was also highlighted by Jahnke et al. in the J. Med. Chem. Perspective «Fragment-to-Lead Medicinal Chemistry Publications in 2019». (https://dx.doi.org/10.1021/acs.jmedchem.0c01608).
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