Discovery of the inhibitors of tumor necrosis factor alpha with structure-based virtual screening

✍ Scribed by Hwanho Choi; Youngseop Lee; Hwangseo Park; Dal-Seok Oh

• Book ID: 104004836
• Publisher: Elsevier Science
• Year: 2010
• Tongue: English
• Weight: 551 KB
• Volume: 20
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/j.bmcl.2010.08.116

✦ Synopsis

Tumor necrosis factor alpha (TNF-a) has been considered as one of the attractive drug targets for allergic diseases including asthma. We have been able to identify five novel TNF-a inhibitors with a drug-design protocol involving the structure-based virtual screening and in vitro cell-based assay for antagonistic activity. Because the newly discovered inhibitors are structurally diverse and have the desirable physicochemical properties as a drug candidate, they deserve a further investigation as anti-asthmatic drugs. The interactions of the identified inhibitors in the binding site of TNF-a dimer are addressed in detail to understand the mechanisms for the stabilization of the inactive dimeric form of TNF-a.