Inhibiting Inflammasomes with Small Molecules

Abstract

Modulation of inflammasomes has tremendous therapeutic potential and is hotly pursued by industry and academia alike. Indeed a growing number of patents are emerging to protect the intellectual property in valuable compound classes. This chapter focusses specifically on the suite of small-molecule NLRP3 inflammasome inhibitors published, as specific modulation of other inflammasomes is not yet well established. Synthetic molecules, known drugs and natural product NLRP3 modulators will be detailed. Some of the molecular classes discussed have been extensively characterised through cell-based screening, pharmacokinetic profiling and therapeutic proof of concept animal models. However, many inhibitors lack rigorous studies and/or have multiple activities of which NLRP3 modulation is only one. While this is not intended as an exhaustive list, it should give an impression of the range of structures and strategies that are being used, alongside challenges encountered, in an effort to exploit the significant therapeutic benefits of targeting inflammasomes.