11β-HSD1 Targeted Library
11β-hydroxysteroid dehydrogenase type I (11β-HSD1, cortisone reductase, HSD11B1, 11beta-hydroxysteroid dehydrogenase type I,11beta-HSD1) is an enzyme that is involved in glucocorticoid regulation by catalyzing the conversion of inactive cortisone to its active form cortisol. These hormones regulate several physiological processes, and modulation of glucocorticoid action has been implicated as a potential treatment for a variety of diseases.
Small-molecule 11β-HSD1 inhibitors are investigated as a treatment for metabolic syndrome, as well as for type 2 diabetes. Several 11β-HSD1 inhibitors are in late preclinical or early clinical development as the next generation of drugs in metabolic syndrome.
OTAVAchemicals 11β-HSD1 Targeted Library (1,060 compounds) has been designed with flexible molecular docking. For the docking, we used crystal structure of human 11β-HSD1 in complex with inhibitor and cofactor NADP (4C7K). The 11β-HSD1 binding pocket in the crystal structure includes bound cofactor which has been preserved during the docking. The most important polar interactions between the cocrystalized ligand and 11β-HSD1 in 4C7K include contacts with Ala172, Ser170 and Tyr183 residues. Presence of hydrogen bonds between docked ligands and these residues has been used as a selection criteria to retain the most promising compounds only. To filter molecular complexes obtained with the docking, a scoring cutoffs based on different scoring functions were used. Finally, the complexes selected with the H-bond and score filtering were subjected to visual analysis in order to discard ligands with improper binding mode.
The library comprises drug-like compounds only.
All the compounds are in stock, cherry-picking is available.
The libraries (DB, SD, XLS, PDF format) as well as the price-list are 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.