Nature Communications (Dec 2019)

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

  • James O’Connell,
  • John Porter,
  • Boris Kroeplien,
  • Tim Norman,
  • Stephen Rapecki,
  • Rachel Davis,
  • David McMillan,
  • Tracy Arakaki,
  • Alex Burgin,
  • David Fox III,
  • Tom Ceska,
  • Fabien Lecomte,
  • Alison Maloney,
  • Alex Vugler,
  • Bruce Carrington,
  • Benjamin P Cossins,
  • Tim Bourne,
  • Alastair Lawson

DOI
https://doi.org/10.1038/s41467-019-13616-1
Journal volume & issue
Vol. 10, no. 1
pp. 1 – 12

Abstract

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While biologics have been successfully applied in TNF antagonist treatments, there are no clinically approved small molecules that target TNF. Here, the authors discover potent small molecule inhibitors of TNF, elucidate their molecular mechanism, and demonstrate TNF inhibition in vitro and in vivo.