PHARMACOTHERAPY

Small-molecule inhibitors get pro-inflammatory TNF into shape

Newly discovered small-molecule TNF inhibitors serve as antagonists of pro-inflammatory TNF signalling by uniquely harnessing the conformational plasticity of trimeric TNF. The development of this approach could mark a resurgence of non-biologic modulators of clinically relevant protein–protein interactions in rheumatology.

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Fig. 1: Mechanisms of action of TNF inhibitors.

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Acknowledgements

S.N.S. is supported by grants from Research Foundation Flanders-Belgium (FWO), Ghent University and VIB, Belgium. D.E. acknowledges support from FWO and VIB.

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Correspondence to Savvas N. Savvides.

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The authors declare no competing interests.

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Savvides, S.N., Elewaut, D. Small-molecule inhibitors get pro-inflammatory TNF into shape. Nat Rev Rheumatol (2020). https://doi.org/10.1038/s41584-020-0388-2

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