Targeting pyroptosis in inflammatory bowel disease: A potentially effective therapeutic approach

Table 2 Biologics of pyroptosis-related proteins

Name	Target protein	Pharmacological mechanism	Pyroptotic diseases	Clinical stage	Ref.
Canakinumab (ilaris)	IL-1β	IL-1β monoclonal antibody, inhibits NLRP3 downstream effects	Cryopyrin-associated periodic syndromes	Phase III completed (SJIA; No. NCT02396212)	Shaul et al[81]; Miyamoto et al[82]
Anakinra	IL-1	Recombinant IL-1 receptor antagonist	Rheumatoid arthritis; Winnie-TNF-KO murine model (IBD)	Phase IV (RA; No. NCT00121043)	Liso et al[83]; Dogan et al[84]; Truyens et al[85]
GSK1070806	IL-18	Humanized monoclonal antibody against IL-18	Rheumatoid arthritis; Crohn’s disease	Phase II (CD; No. NCT03681067)	Guha et al[86]
DFV890	NLRP3	Oral NLRP3 inhibitor (small molecule biologic)	Coronary heart disease; COVID-19	Phase II (COVID-19; No. NCT04382053)	Shen et al[87]; Gatlik et al[88]; Madurka et al[89]
NLRP3-ASO	NLRP3 mRNA	Antisense oligonucleotide suppressing NLRP3	Cryopyrin-associated periodic syndromes; Alzheimer’s disease	Preclinical	Kaufmann et al[90]; Braatz et al[91]
IC100 (ASC-mAb)	ASC speck	Monoclonal antibody blocking inflammasome assembly	Retinopathy of prematurity; Parkinson’s disease	Preclinical	de Rivero Vaccari et al[92]; Yuan et al[93]; Cyr et al[94]
Caspase-1 siRNA	Caspase-1 mRNA	siRNA silencing caspase-1 expression	Alzheimer’s disease	Preclinical	Han et al[95]
GSDMD-Nb	GSDMD	Nanobody binding GSDMD-N terminus to prevent pore formation	Sepsis	Preclinical	Schiffelers et al[96]

Detailed information regarding primary endpoints and adverse reactions for these biologics is selectively summarized in the corresponding agent profiles within the “biologics: Next-generation targeted intervention approaches” subsection of the main text.

NLRP3: Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3; ASC: Adapter protein apoptosis-associated speck-like protein containing a CARD; IL: Interleukin; ASO: Antisense oligonucleotide; siRNA: Small interfering RNA; GSDMD: Gasdermin D; mRNA: Messenger RNA; TNF: Tumor necrosis factor; KO: Knockout; IBD: Inflammatory bowel disease; COVID-19: Coronavirus disease 2019; SJIA: Systemic juvenile idiopathic arthritis; CD: Crohn’s disease; RA: Rheumatoid arthritis.