LSD1-Based Reversible Inhibitors Virtual Screening and Binding Mechanism Computational Study.

ABSTRACT: As one of the crucial targets of epigenetics, histone lysine-specific demethylase 1 (LSD1) is significant in the occurrence and development of various tumors. Although several irreversible covalent LSD1 inhibitors have entered clinical trials, the large size and polarity of the FAD-binding pocket and undesired toxicity have focused interest on developing reversible LSD1 inhibitors. In this study, targeting the substrate-binding pocket of LSD1, structure-based and ligand-based virtual screenings were adopted to expand the potential novel structures with molecular docking and pharmacophore model strategies, respectively. Through drug-likeness evaluation, ADMET screening, molecular dynamics simulations, and binding free energy screening, we screened out one and four hit compounds from the dat

SUBMITTER: Yin Z 

PROVIDER: S-EPMC10383809 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature