Combination of <i>In Silico</i> and <i>In Vitro</i> Screening to Identify Novel Glutamate Carboxypeptidase II Inhibitors.

ABSTRACT: Glutamate carboxypeptidase II (GCPII) is a metalloprotease implicated in neurological diseases and prostate oncology. While several classes of potent GCPII-specific inhibitors exist, the development of novel active scaffolds with different pharmacological profiles remains a challenge. Virtual screening followed by in vitro testing is an effective means for the discovery of novel active compounds. Structure- and ligand-based pharmacophore models were created based on a dataset of known GCPII-selective ligands. These models were used in a virtual screening of the SPECS compound library (∼209.000 compounds). Fifty top-scoring virtual hits were further experimentally tested for their ability to inhibit GCPII enzymatic activity in vitro. Six hits were found to have moderate to hig

SUBMITTER: Temml V 

PROVIDER: S-EPMC9976286 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature