Development of a characterised tool kit for the interrogation of NLRP3 inflammasomedependent responses

Elena Redondo Castro, Dorte Faust, Simon Fox, Alex Baldwin, Simon Osborne, Michael Haley, E Karran, Hugh Nuthall, Peter J Atkinson, Lee A Dawson, Carol Routledge, Stuart Allan, Sally Freeman, Janet Brownlees, David Brough

Research output: Contribution to journalArticlepeer-review


Inflammation is an established contributor to disease and the NLRP3 inflammasome is emerging as a potential therapeutic target. A number of small molecule inhibitors of the NLRP3 pathway have been described. Here we analysed the most promising of these inhibitor classes side by side to assess relative potency and selectivity for their respective putative targets.
Assessed using ASC inflammasome-speck formation, and release of IL-1β, in both human monocyte/macrophage THP1 cells and in primary mouse microglia, we compared the relative potency and selectivity of P2X7 inhibitors, inflammasome inhibitors (diarylsulfonylurea vs. the NBC series), and caspase-1 inhibitors. In doing so we are now able to provide a well characterised small molecule tool kit for interrogating and validating inflammasome-dependent
responses with a range of nanomolar potency inhibitors against established points in the inflammasome pathway.
Original languageEnglish
JournalScientific Reports
Early online date4 Apr 2018
Publication statusPublished - 2018


  • P2X7 receptor
  • Nlrp3 inflammasome
  • Interleukin-1
  • caspase-1
  • inflammation

Research Beacons, Institutes and Platforms

  • Manchester Institute for Collaborative Research on Ageing


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