Structure-Based Virtual Screening for Low Molecular Weight Chemical Starting Points for Dipeptidyl Peptidase IV Inhibitors

摘要

Structure-based virtual screening was performed against the target dipeptidyl peptidase IV(DPP-IV)to identify good chemical starting points for medicinal chemistry.A database of available compounds was filtered by calculated physical properties and undesired chemistry.This database was matched against two in-house designed DPP-IV pharmacophores,and the hits from these pharmacophore searches were docked into a DPP-IV crystal structure.Compounds were then selected for testing and 51 active compounds were identified from a list of 4000 compounds tested.These had activities ranging from 30% to 82% when tested at a concentration of 30 muM in an enzyme inhibition assay.