A metal-based inhibitor of tumor necrosis factor-α.
Staying in the pocket: A cyclometalated iridium(III) biquinoline complex targets the protein-protein interface (see picture; C yellow, N blue, Ir dark green) of the tumor necrosis factor-α (TNF-α) trimer. Molecular-modeling studies confirm the nature of this interaction. Both enantiomers of the iridium complex display comparable in vitro potency to the strongest small-molecule inhibitor of TNF-α.
Institute of Chinese Medical Sciences and State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macao, SAR China. duncanleung@umac.mo
Chung-Hang
CH
Leung
Hai-Jing
HJ
Zhong
Hui
H
Yang
Zhen
Z
Cheng
Daniel Shiu-Hin
DS
Chan
Victor Pui-Yan
VP
Ma
Ruben
R
Abagyan
Chun-Yuen
CY
Wong
Dik-Lung
DL
Ma
D001665:Binding Sites; D056831:Coordination Complexes / Q000737:chemistry*; D018360:Crystallography, X-Ray; D056945:Hep G2 Cells; D006801:Humans; D055767:Immobilized Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D007495:Iridium / Q000737:chemistry*; D060066:Protein Interaction Maps; D017434:Protein Structure, Tertiary; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D013237:Stereoisomerism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
D056831:Coordination Complexes; D055767:Immobilized Proteins; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D007495:Iridium