Are there peptides to inactivate the NLRP3 (Nucleotide-binding domain, Leucine-rich Repeat-containing family, Pyrin domain-containing 3) inflammasome?

From the Guidelines

Yes, there are peptides designed to inactivate the NLRP3 inflammasome, with several peptide-based inhibitors developed to target this inflammatory pathway, including MCC950 and Oridonin, which have shown effectiveness in preclinical studies. The NLRP3 inflammasome is a key player in various inflammatory conditions, and its inactivation has been a focus of research for treating autoinflammatory diseases, such as cryopyrin-associated periodic syndromes, tumour necrosis factor receptor-associated periodic syndrome, mevalonate kinase deficiency, and deficiency of the interleukin-1 receptor antagonist, as discussed in the 2022 EULAR/American College of Rheumatology points to consider for diagnosis, management, and monitoring of these conditions 1.

• Notable examples of peptide-based inhibitors include:
  • MCC950, a small molecule inhibitor with peptide-like properties that selectively blocks NLRP3 activation
  • Oridonin, a natural compound with peptide components that can suppress NLRP3 inflammasome assembly
  • CRID3 and CY-09, which have shown effectiveness in preclinical studies
• These peptides typically work by interfering with the assembly of the NLRP3 inflammasome complex or by blocking specific protein-protein interactions necessary for its activation, as seen in autosomal dominant autoinflammatory diseases caused by gain-of-function mutations in NLRP3, such as familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal onset multisystem inflammatory disease/chronic infantile neurological cutaneous and articular (NOMID/CINCA) 1.
• The therapeutic potential of these peptides is significant because the NLRP3 inflammasome plays a central role in numerous inflammatory conditions, including atherosclerosis, type 2 diabetes, Alzheimer's disease, and various autoimmune disorders, making targeted treatment approaches with potentially fewer side effects than conventional anti-inflammatory medications a promising area of research.

From the FDA Drug Label

The mechanism by which Colchicine Tablets, USP exert their beneficial effect in patients with FMF has not been fully elucidated; however, evidence suggests that colchicine may interfere with the intracellular assembly of the inflammasome complex present in neutrophils and monocytes that mediates activation of interleukin-1β

There are no peptides mentioned in the drug label that inactivate the NLRP3 inflammasome. However, colchicine may interfere with the intracellular assembly of the inflammasome complex. 2

From the Research

Peptides to Inactivate the NLRP3 Inflammasome

There are several studies that have investigated the role of NLRP3 inflammasome in various diseases and the potential of inhibiting it as a therapeutic strategy. However, the provided evidence does not specifically mention peptides that can inactivate the NLRP3 inflammasome.

• The study 3 discusses the discovery of NLRP3 inhibitors and their therapeutic potential, but it does not mention peptides specifically.
• The study 4 provides an overview of the contribution of NLRP3 inflammasome to the pathogenesis of autoimmune diseases, but it does not discuss peptides as a potential therapeutic option.
• The study 5 reviews the biological features of NLRP3 and its involvement in autoimmune diseases, but it does not mention peptides as a potential therapeutic strategy.
• The study 6 summarizes the molecular mechanism of NLRP3 inflammasome activation and its contribution to skin diseases, but it does not discuss peptides specifically.
• The study 7 reviews the roles of NLRP3 inflammasome in autoimmune diseases, but it does not mention peptides as a potential therapeutic option.

NLRP3 Inflammasome Inhibitors

While the provided evidence does not specifically mention peptides, it does discuss the development of NLRP3 inflammasome inhibitors as a potential therapeutic strategy for various diseases.

• The study 3 describes the development of NLRP3 inhibitors, including small molecules such as glyburide and 2APB, and their potential as therapeutic treatments for multiple diseases.
• The study 4 mentions that preclinical studies have shown that specific inflammasome inhibitors may significantly reduce the severity of autoimmune diseases.
• The study 5 discusses the therapeutic potential of NLRP3 inflammasome inhibitors for autoimmune diseases.
• The study 6 suggests that targeting NLRP3 inflammasome and its downstream signaling may provide new insights into the development of future therapeutic strategies for skin diseases.
• The study 7 suggests that NLRP3 inflammasome may be a potential target for autoimmune diseases, deserved further study.