Discovery of Novel Ligands for TNF-α and TNF Receptor-1 through Structure-Based Virtual Screening and Biological Assay.

ABSTRACT: Tumor necrosis factor α (TNF-α) is overexpressed in various diseases, and it has been a validated therapeutic target for autoimmune diseases. All therapeutics currently used to target TNF-α are biomacromolecules, and limited numbers of TNF-α chemical inhibitors have been reported, which makes the identification of small-molecule alternatives an urgent need. Recent studies have mainly focused on identifying small molecules that directly bind to TNF-α or TNF receptor-1 (TNFR1), inhibit the interaction between TNF-α and TNFR1, and/or regulate related signaling pathways. In this study, we combined in silico methods with biophysical and cell-based assays to identify novel antagonists that bind to TNF-α or TNFR1. Pharmacophore model filtering and molecular docking were applied to identify potent

SUBMITTER: Chen S 

PROVIDER: S-EPMC6732210 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature