title: Direct Rel/NF-κB inhibitors: structural basis for mechanism of action.
abstract: The Rel/NF-κB transcription factors have emerged as novel therapeutic targets for a variety of human diseases and pathological conditions, including inflammation, autoimmune diseases, cancer, ischemic injury, osteoporosis, transplant rejection and neurodegeneration. Several US FDA-approved drugs may, in part, attribute their therapeutic effects to the inhibition of the Rel/NF-κB pathway. Strategies for blocking the Rel/NF-κB signaling pathway have inspired the pharmaceutical industry to develop inhibitors for I-κB kinase, however, this article focuses instead on identifying natural compounds that directly target and inhibit DNA binding and transcription activity of Rel/NF-κB. These include compounds containing a quinone core, an α,β unsaturated carbonyl and a benzene diamine. By investigating the mechanisms of action of existing natural inhibitors, novel strategies and synthetic approaches can be devised that will facilitate the development of novel and selective Rel/NF-κB inhibitors with better safety profiles.
authors.affiliation: Division of Immunology, Department of Medicine, Weill Medical College, Cornell University, 407 East 61st Street, RR-506, NY 10065, USA.
authors.forename: Samedy
authors.initials: S
authors.lastname: Ouk
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Liou
authors.forename: Hsiou-Chi
authors.initials: HC
authors.lastname: Liou
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D007659:Ketones / Q000737:chemistry / Q000627:therapeutic use; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D011809:Quinones / Q000737:chemistry / Q000627:therapeutic use; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D007659:Ketones; D016328:NF-kappa B; D011809:Quinones; D051996:Transcription Factor RelA; D051550:I-kappa B Kinase