Therapeutic modulation of inflammasome pathways

2020/08/07 by Dhruv Chauhan, Lieselotte Vande Walle, Mohamed Lamkanfi · 1 citation
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · #IL-33, ST2, and ILC Pathways #Inflammasome and immune disorders #Macrophage Migration Inhibitory Factor

paper · pdf · doi:10.1111/imr.12908

openalex publication_date 2020/08/07 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/29

Abstract

Inflammasomes are macromolecular complexes formed in response to pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) that drive maturation of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18, and cleave gasdermin D (GSDMD) for induction of pyroptosis. Inflammasomes are highly important in protecting the host from various microbial pathogens and sterile insults. Inflammasome pathways are strictly regulated at both transcriptional and post-translational checkpoints. When these checkpoints are not properly imposed, undue inflammasome activation may promote inflammatory, metabolic and oncogenic processes that give rise to autoinflammatory, autoimmune, metabolic and malignant diseases. In addition to clinically approved IL-1-targeted biologics, upstream targeting of inflammasome pathways recently gained interest as a novel pharmacological strategy for selectively modulating inflammasome activation in pathological conditions.

Citations

• A clinical perspective of IL‐1β as the gatekeeper of inflammation
• Cutting Edge: NF-κB Activating Pattern Recognition and Cytokine Receptors License NLRP3 Inflammasome Activation by Regulating NLRP3 Expression
• Glyburide inhibits the Cryopyrin/Nalp3 inflammasome
• (S)-1-((S)-2-[1-(4-Amino-3-chloro-phenyl)-methanoyl]-amino-3,3-dimethyl-butanoyl)-pyrrolidine-2-carboxylic acid ((2 R,3 S)-2-ethoxy-5-oxo-tetrahydro-furan-3-yl)-amide (VX-765), an Orally Available Selective Interleukin (IL)-Converting Enzyme/Caspase-1 Inhibitor, Exhibits Potent Anti-Inflammatory Activities by Inhibiting the Release of IL-1β and IL-18
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Cited by

• Degrading the key component of the inflammasome: development of an NLRP3 PROTAC

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