title: Discovery of the inhibitors of tumor necrosis factor alpha with structure-based virtual screening.
abstract: Tumor necrosis factor alpha (TNF-α) has been considered as one of the attractive drug targets for allergic diseases including asthma. We have been able to identify five novel TNF-α 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-α dimer are addressed in detail to understand the mechanisms for the stabilization of the inactive dimeric form of TNF-α.
authors.affiliation: Department of Bioscience and Biotechnology, Sejong University, 98 Kunja-dong, Kwangjin-ku, Seoul 143-747, Republic of Korea.
authors.forename: Hwanho
authors.initials: H
authors.lastname: Choi
authors.forename: Youngseop
authors.initials: Y
authors.lastname: Lee
authors.forename: Hwangseo
authors.initials: H
authors.lastname: Park
authors.forename: Dal-Seok
authors.initials: DS
authors.lastname: Oh
mesh_terms: D000465:Algorithms; D018927:Anti-Asthmatic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D018927:Anti-Asthmatic Agents; D014409:Tumor Necrosis Factor-alpha