title: Small-molecule inhibitors of the interaction between TNF and TNFR.
abstract: The overexpression of TNF has been implicated in a variety of disease conditions including rheumatoid arthritis, Crohn's disease, HIV and cancer. It is presently a therapeutic target for inflammatory diseases. Many of the therapeutics currently used are biologics designed to sequester TNF, preventing it from binding with its receptors. Recent research has been focused on finding small molecules that alter the production of TNF, modulate its signal transduction pathways, or directly inhibit the binding to its receptors. Modulation of a protein-protein interaction with small molecules is an interesting and nontrivial approach. The various strategies used in obtaining small-molecule, nonpeptide, inhibitors of the TNF-TNF receptor interaction through disruption of the TNF trimer or direct inhibition of the TNF-TNF receptor interaction are presented here.
authors.affiliation: Fairfield University, 173 North Benson Road, Fairfield, CT 06824, USA. jmdavis@fairfield.edu
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Davis
authors.forename: Julie
authors.initials: J
authors.lastname: Colangelo
mesh_terms: D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D054852:Small Molecule Libraries; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism
chemical_list: D018124:Receptors, Tumor Necrosis Factor; D054852:Small Molecule Libraries; D014409:Tumor Necrosis Factor-alpha