Discovery of the inhibitors of tumor necrosis factor alpha with structure-based virtual screening.
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.
Choi
Hwanho
H
Department of Bioscience and Biotechnology, Sejong University, 98 Kunja-dong, Kwangjin-ku, Seoul 143-747, Republic of Korea.
Lee
Youngseop
Y
Park
Hwangseo
H
Oh
Dal-Seok
DS
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*
D018927:Anti-Asthmatic Agents; D014409:Tumor Necrosis Factor-alpha