In Silico Discovery of Plant-Origin Natural Product Inhibitors of Tumor Necrosis Factor (TNF) and Receptor Activator of NF-κB Ligand (RANKL).

ABSTRACT: An in silico drug discovery pipeline for the virtual screening of plant-origin natural products (NPs) was developed to explore new direct inhibitors of TNF and its close relative receptor activator of nuclear factor kappa-B ligand (RANKL), both representing attractive therapeutic targets for many chronic inflammatory conditions. Direct TNF inhibition through identification of potent small molecules is a highly desired goal; however, it is often hampered by severe limitations. Our approach yielded a priority list of 15 NPs as potential direct TNF inhibitors that were subsequently tested in vitro against TNF and RANKL. We thus identified two potent direct inhibitors of TNF function with low micromolar IC₅₀ values and minimal toxicity even at high concentrations. Most

SUBMITTER: Melagraki G 

PROVIDER: S-EPMC6068282 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature