Repurposing Drugs for Inhibition against ALDH2 via a 2D/3D Ligand-Based Similarity Search and Molecular Simulation.

ABSTRACT: Aldehyde dehydrogenase-2 (ALDH2) is a crucial enzyme participating in intracellular aldehyde metabolism and is acknowledged as a potential therapeutic target for the treatment of alcohol use disorder and other addictive behaviors. Using previously reported ALDH2 inhibitors of Daidzin, CVT-10216, and CHEMBL114083 as reference molecules, here we perform a ligand-based virtual screening of world-approved drugs via 2D/3D similarity search methods, followed by the assessments of molecular docking, toxicity prediction, molecular simulation, and the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) analysis. The 2D molecular fingerprinting of ECFP4 and FCFP4 and 3D molecule-shape-based USRCAT methods show good performances in selecting compounds with a strong binding behavior with ALDH

SUBMITTER: Jiang W 

PROVIDER: S-EPMC10650273 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature