NLRP3-IN-75
NLRP3-IN-75 is an orally active NLRP3 inhibitor. NLRP3-IN-75 suppresses IL-1β secretion (IC50 = 23 nM). NLRP3-IN-75 selectively inhibits NLRP3 activation by disrupting inflammasome assembly without affecting NLRC4 or AIM2 inflammasomes. NLRP3-IN-75 exhibits superior efficacy in acute peritonitis, diabetic kidney disease and IBD models.
For research use only. We do not sell to patients.
- Formula: C20H30N4O3S
- Molecular Weight:406.54
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
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IL-1β 23 nM (IC50) |
In Vitro
NLRP3-IN-75 (Compound 15) (0.03-100 μM, 30 min) significantly inhibits IL-1β release in LPS- and ATP-stimulated BMDM cells (IC50 = 0.106 μM) and THP-1 cells (IC50 = 23 nM)[1].
NLRP3-IN-75 (10 μM, 4 h) shows selectivity for NLRP3 inflammasome by maintaining IL-1β secretion in the NLRC4 or AIM2 inflammasome pathways in flagellin-transfected BMDM cells[1].
NLRP3-IN-75 (10 μM, 4 h) does not affect the initiation phase of NLRP3 inflammation activation as TNF-α and IL-6 production maintains[1].
NLRP3-IN-75 (10 μM, 4 h) obstructs the interaction between NLRP3 and ASC induced by LPS and ATP in BMDM cells by impeding NLRP3 inflammasome assembly[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
Parmacokinetics
In Vivo
NLRP3-IN-75 (20 mg/kg, p.o., 6 weeks) mitigates HFD- and STZ-induced DKD in mice by targeting the NLRP3 inflammasome [1].
NLRP3-IN-75 (0.2-5 mg/kg, p.o., 10 days) ameliorates the DSS (HY-116282C)-induced inflammatory bowel disease in mice models[1].
NLRP3-IN-75 (20 mg/kg, p.o., a single dose) shows low potential for cardiovascular or pulmonary toxicity in mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:LPS (HY-D1056) (15 mg/kg, i.p.)- and ATP (1 mM/kg, i.p.)-induced acute peritonitis mice (6-8 weeks old, male C57BL/6J)[1]
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Dosage:1 mg/kg, 20 mg/kg
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Administration:Oral gavage (p.o.)
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Result:Achieved 100% survival rate in LPS-induced followed by ATP-induced acute peritonitis mice models.
Suppressed serum IL-1β level in peritonitis mice models 12 h post-ATP administration, and presented better effect with increasing dose.
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Animal Model:Male C57BL/6J HFD (4 weeks)- and STZ (HY-13753) (50 mg/kg, i.p., 5 days)-induced diabetic kidney disease (DKD) mice (n = 5-6, 20-22 g)[1]
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Dosage:20 mg/kg, 6 weeks
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Administration:Oral gavage (p.o.), 6 weeks; administered after STZ and HFD feeding
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Result:Significantly reduced the elevated urine albumin-to-creatinine ratio (UACR) caused by the HFD- and STZ-induced DKD mice models.
Ameliorated the thickening of the glomerular and tubular basement membranes in DKD models.
Decreased inflammatory cytokine IL-1β but no effect on TNF-α level[1].
Reduced macrophage infiltration.
Disrupted the NLRP3-ASC interaction.
Reduced LDL-C levels without affecting HDL-C levels.
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Animal Model:2% (w/v) DSS (HY-116282C) (7 days) in distilled water-induced colitis mice (Male C57BL/6J, n = 5-10, 20-22 g)[1]
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Dosage:0.2 or 5 mg/kg
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Administration:Oral gavage (p.o.) , 9 days (day 1-day 10)
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Result:Attenuated weight loss in DSS-induced acute colitis mice models.
Reduced fecal bleeding and decreased disease activity index (DAI) scores.
Ameliorated pathological features such as disruption of mucosal barrier, crypt necrosis, substantial depletion of the mucosal barrier, crypt necrosis, substantial depletion of goblet cells, and pronounced infiltration of inflammatory cells.
Inhibited colonic IL-1β without affecting TNF-α level.
Chemical Information
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Molecular Weight 406.54
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Formula C20H30N4O3S
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SMILES
O=C(NC1=C2CCCC2=CC3=C1CCC3)NS(N(C4CCN(CC4)C)C)(=O)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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DSS-Induced Colitis
Dextran sulfate sodium (DSS)-induced colitis is generated by administering DSS in mouse drinking water, producing epithelial injury, barrier disruption, weight loss, diarrhea, fecal blood, colon shortening, histologic mucosal damage, and inflammatory mediator changes; the model is mainly used to study acute or chronic intestinal inflammation resembling selected features of ulcerative colitis. DSS injury is interpreted through clinical and tissue readouts rather than a single molecular endpoint: daily body weight, stool consistency, and bleeding are combined into a disease activity index, while colon length, histology, cytokines, myeloperoxidase activity, intestinal permeability, and tight-junction markers provide complementary measures of inflammation and barrier damage.
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TNBS-Induced Colitis
TNBS-induced colitis is produced by intrarectal delivery of 2,4,6-trinitrobenzene sulfonic acid in ethanol, where ethanol disrupts the mucosal barrier and TNBS haptenates colonic proteins, generating immune-mediated colonic inflammation with weight loss, diarrhea, ulceration, transmural injury, inflammatory-cell infiltration, and cytokine responses. The model is used as an experimental intestinal inflammation model with Crohn’s disease–like features, especially when Th1-type responses, IL-12–dependent inflammation, chronic relapsing inflammation, or fibrosis-related endpoints are studied.
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Zymosan-Induced Peritonitis
Zymosan-induced peritonitis is a sterile acute-inflammation model produced by intraperitoneal injection of zymosan, a yeast cell-wall particle preparation, followed by quantification of leukocyte recruitment and soluble inflammatory mediators in peritoneal lavage fluid. Low-dose zymosan peritonitis is commonly used as a self-resolving acute inflammation model in which neutrophil recruitment occurs early and monocyte/macrophage accumulation follows later. The assay readouts include total peritoneal leukocyte number, differential neutrophil and monocyte/macrophage counts, peritoneal cytokines and chemokines, plasma or peritoneal exudation, and optional lipidomic or metabolomic changes during inflammation and resolution. Early neutrophil recruitment after zymosan depends strongly on complement and mast-cell C5a receptor signaling, whereas later monocyte recruitment is linked to MCP-1/CCL2 production.
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Pyroptosis Solutions
Pyroptosis is a lytic inflammatory cell-death pathway executed by gasdermin pores, most classically through inflammasome-mediated activation of caspase-1, cleavage of gasdermin D, membrane pore formation, LDH release, and secretion of IL-1β and IL-18. The canonical pathway is commonly modeled by priming cells with an inflammatory signal such as LPS to induce pro-IL-1β and inflammasome components, followed by an activation signal such as ATP or nigericin to activate NLRP3, ASC speck formation, caspase-1 cleavage, GSDMD cleavage, cytokine release, and pyroptotic membrane rupture. The non-canonical pathway is triggered when cytosolic LPS activates mouse caspase-11 or human caspase-4/5, leading to GSDMD cleavage and pyroptosis, and this can secondarily activate NLRP3-dependent IL-1β release. Pyroptosis is linked to inflammatory injury, infection, cancer, liver disease, ocular disease, placental inflammation, and other disease phenotypes, but unresolved questions include which gasdermin fam
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
NLRP3-IN-75 Related Classifications
HY-170233 Related Classifications
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