title: Anti-TNF-alpha therapies: the next generation.
abstract: The functioning of the immune system is finely balanced by the activities of pro-inflammatory and anti-inflammatory mediators or cytokines. Unregulated activities of these mediators can lead to the development of serious inflammatory diseases. In particular, enhanced tumour-necrosis factor-alpha (TNF-alpha) synthesis is associated with the development of rheumatoid arthritis, psoriatic arthritis and inflammatory bowel disease. Inhibiting TNF-alpha activities in these diseases has been remarkably successful. However, the current injectable protein therapies have associated risks and limitations. An oral, small molecule that regulates TNF-alpha biology could either replace the injectables or provide better disease control when used alone or in conjunction with existing therapies. In this review, we discuss briefly the present understanding of TNF-alpha-mediated biology and the current injectable therapies in clinical use, and focus on some of the new therapeutic approaches with oral, small-molecule inhibitors.
authors.affiliation: Nereus Pharmaceuticals, 10480 Wateridge Circle, San Diego, California 92121, USA. mpalladino@nereuspharm.com
authors.forename: Michael A
authors.initials: MA
authors.lastname: Palladino
authors.forename: Frances Rena
authors.initials: FR
authors.lastname: Bahjat
authors.forename: Emmanuel A
authors.initials: EA
authors.lastname: Theodorakis
authors.forename: Lyle L
authors.initials: LL
authors.lastname: Moldawer
mesh_terms: D000818:Animals; D006801:Humans; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D047889:Receptors, Tumor Necrosis Factor, Type II; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013678:Technology, Pharmaceutical / Q000639:trends; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; D047889:Receptors, Tumor Necrosis Factor, Type II; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha