Virtual Screening Strategy and In Vitro Tests to Identify New Inhibitors of the Immunoproteasome.

ABSTRACT: Immunoproteasome inhibition is a promising strategy for the treatment of hematological malignancies, autoimmune diseases, and inflammatory diseases. The design of non-covalent inhibitors of the immunoproteasome β1i/β5i catalytic subunits could be a novel approach to avoid the drawbacks of the known covalent inhibitors, such as toxicity due to off-target binding. In this work, we report the biological evaluation of thirty-four compounds selected from a commercially available collection. These hit compounds are the outcomes of a virtual screening strategy including a dynamic pharmacophore modeling approach onto the β1i subunit and a pharmacophore/docking approach onto the β5i subunit. The computational studies were first followed by in vitro enzymatic assays at 100 μM. Only compounds capable

SUBMITTER: Culletta G 

PROVIDER: S-EPMC10341482 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature