In Search of Selective 11?-HSD 1 Inhibitors without Nephrotoxicity. An Approach to Resolve the Metabolic Syndrome by Virtual Based Screening

      Аннотация: Over expression of 11?-HSD 1 in key metabolic tissues is related to the development of type 2 diabetes, obesity, hypertension and metabolic syndrome. Nephrotoxicity of corosolic acid (selective inhibitor of 11?-HSD 1) is recently reported, which is one of the major drawback. Therefore, it is of great interest to find out the selective 11?-HSD 1 inhibitors without nephrotoxicity. Using crystal structures of 11?-HSD 1 in complex with inhibitors as a source of structural information, a combined structure-based virtual screening approach followed by PASS toxicity prediction, Lipinski’s rule and ADME prediction implemented to find out the potent and selective 11 ?-HSD 1 analog of corosolic acid without nephrotoxicity.

Ключевые слова: ADME, Virtual screening, 11?-HSD 1, PASS toxicity, Lipnski’s Rule