Virtual screening-based identification of lead molecules as selective TACE inhibitors

Abstract

Some novel selective inhibitors of tumor necrosis factor-α converting enzyme (TACE) have been identified from virtual screening of Asinex database containing 2,06,759 compounds using HTS docking with TACE and MMPs and application of Lipinski’s rule of five. Docking studies were carried out for known inhibitors along with lead compounds. Pyrrolidine-based tartrate diamides were docked into the active site of TACE along with MMPs to get insight regarding the binding interactions of active and inactive TACE inhibitors. The 3D orientations of the obtained hits from virtual screening were found to match with that of known inhibitors supporting the binding of the hit molecules into the active site of TACE.