The enzyme 3-hydroxy-3-methyl-glutaryl-CoA reductase (3-hydroxy-3-methylglutaryl-coenzyme A, HMG-CoA, HMGCR) catalyzes the conversion of HMG-CoA to mevalonate, an early and rate-limiting step in cholesterol biosynthesis. The HMG-CoA reductase inhibitors, also known as statins, are the most effective class of drugs for lowering serum low-density lipoprotein cholesterol concentrations.
The HMG-CoA Reductase Targeted Library (514 compounds in total) was designed with combined receptor-based and ligand-based approach. For receptor-based approach, crystal structure of HMG-CoA reductase (PDB ID: 2R4F) was used. Ligand-based approach employed training set of known HMG-CoA reductase inhibitors taken from ChEMBL database. The input compounds (OTAVAchemicals Drug-like Green Collection) have been ranged by physicochemical parameters of known HMG-CoA reductase inhibitors and then screened independently using molecular docking, receptor based pharmacophore search and 3D-QSAR ligand-based models. Obtained molecular docking complexes were filtered based on docking score cut-off and inspection of intermolecular hydrophobic contacts/ hydrogen bonds with key active site’s residues. As a result, two subsets of compounds were created: the first subset comprises compounds obtained with molecular docking and pharmacophore method, and the second subset represents compounds resulted from molecular docking and 3d-QSAR method. Both subsets were visually inspected to avoid ligands with incorrect binding mode.
This library comprises drug-like compounds only and provides an excellent basis for research and drug discovery aimed at cholesterol level management.
All compounds are in stock, cherry-picking is available.
The library (DB, SD, XLS, PDF format) as well as the price-list is available on request. Feel free to contact us or use on-line form below to send an inquiry if you are interested to obtain this library or if you need more information.