Small molecules that inhibit TNF signalling by stabilising an asymmetric form of the trimer

Tumour necrosis factor (TNF) is a cytokine belonging to a family of trimeric proteins; it has been shown to be a key mediator in autoimmune diseases such as rheumatoid arthritis and Crohn’s disease. While TNF is the target of several successful biologic drugs, attempts to design small molecule thera...

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Bibliographic Details
Published in:	Nature communications Vol. 10; no. 1; pp. 5795 - 12
Main Authors:	O’Connell, James, Porter, John, Kroeplien, Boris, Norman, Tim, Rapecki, Stephen, Davis, Rachel, McMillan, David, Arakaki, Tracy, Burgin, Alex, Fox III, David, Ceska, Tom, Lecomte, Fabien, Maloney, Alison, Vugler, Alex, Carrington, Bruce, Cossins, Benjamin P, Bourne, Tim, Lawson, Alastair
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 19.12.2019 Nature Publishing Group Nature Portfolio
Subjects:	631/154/309/2144 631/154/309/2420 631/154/309/507 Animals Anti-Inflammatory Agents - pharmacology Anti-Inflammatory Agents - therapeutic use Arthritis Arthritis, Experimental - drug therapy Arthritis, Experimental - immunology Asymmetry Autoimmune diseases Cell Line Crohn's disease Crystallography, X-Ray Cytokines Drug development Drug Discovery Drugs Humanities and Social Sciences Male Mice Molecular Dynamics Simulation multidisciplinary Neutrophil Infiltration - drug effects Neutrophils - drug effects Neutrophils - immunology Protein interaction Protein Multimerization - drug effects Protein Stability - drug effects Protein Structure, Quaternary - drug effects Proteins Receptors, Tumor Necrosis Factor, Type I - immunology Receptors, Tumor Necrosis Factor, Type I - metabolism Recombinant Proteins - isolation & purification Recombinant Proteins - metabolism Recombinant Proteins - ultrastructure Rheumatoid arthritis Science Science (multidisciplinary) Signal Transduction - drug effects Signal Transduction - immunology Signaling Structure-Activity Relationship Treatment Outcome Trimers Tumor necrosis factor Tumor Necrosis Factor-alpha - antagonists & inhibitors Tumor Necrosis Factor-alpha - immunology Tumor Necrosis Factor-alpha - isolation & purification Tumor Necrosis Factor-alpha - metabolism Tumor Necrosis Factor-alpha - ultrastructure Tumor necrosis factor-TNF Tumors
ISSN:	2041-1723, 2041-1723
Online Access:	Get full text
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