Boron based inhibitors of the NLRP3 inflammasome

Alex Baldwin, Jack Rivers-Auty, Michael Daniels, Claire White, Carl H. Schwalbe, T. Schilling, Halah Hammadi, Panichakorn Jaiyong, Nicholas G. Spencer, Hazel England, Nadia M. Luheshi, Manikandan Kadirvel, Catherine B. Lawrence, Nancy Rothwell, Michael Harte, Richard Bryce, Stuart Allen, Claudia Eder, Sally Freeman, David Brough

Research output: Contribution to journalArticlepeer-review


NLRP3 is a receptor important for host responses to infection, yet also known to contribute to devastating diseases such as Alzheimer’s disease, diabetes, atherosclerosis and others, making inhibitors for NLRP3 sought after. One of the inhibitors currently in use is 2-aminoethoxy diphenylborinate (2APB). Unfortunately, in addition to inhibiting NLRP3, 2APB also displays non-selective effects on cellular Ca2+ homeostasis. Here, we use 2APB as a chemical scaffold to build a series of inhibitors, the NBC series, that inhibit NLRP3 inflammasome in vitro and in vivo without affecting Ca2+ homeostasis. The core chemical insights of this work is that oxazaborine ring is a critical feature of the NBC series, and the main biological insight that the use of NBC inhibitors led to was that NLRP3 inflammasome activation was independent of Ca2+. The NBC compounds represent useful tools to dissect NLRP3 function, and may lead to oxazaborine ring containing therapeutics.
Original languageEnglish
Pages (from-to)1321-1335
Number of pages15
JournalCell Chemical Biology
Issue number11
Early online date21 Sept 2017
Publication statusPublished - 16 Nov 2017

Research Beacons, Institutes and Platforms

  • Lydia Becker Institute


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