NLRP3-IN-96
NLRP3-IN-96 is a blood-brain barrier-penetrant NLRP3 inhibitor with a human Kd value of 556 nM. NLRP3-IN-96 inhibits NLRP3 inflammasome activation, suppresses IL-1β release and reduces NLRP3 expression, and inhibits TNF-α production through an NLRP3-independent pathway. NLRP3-IN-96 can be used for research on neuropathic pain.
For research use only. We do not sell to patients.
- CAS No.: 3113161-60-4
- Formula: C23H26ClFN4O2
- Molecular Weight:444.93
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
IC50 & Target
[1]|
NLRP3 556 nM (Kd) |
IL-1β |
TNF-α |
In Vitro
NLRP3-IN-96 (compound 22) selectively inhibits NLRP3 inflammasome-mediated IL-1β release in J774A.1 macrophages with an IC50 of 70 nM, and is selective over NLRC4 and AIM2 inflammasomes[1].
NLRP3-IN-96 (1-10 μM; 24 h) reduces NLRP3 expression in AD-derived hiPSC-microglia stimulated with oAβ or TNFα/IFNγ[1].
NLRP3-IN-96 (1 μM; 24 h) reduces NLRP3 expression in hiPSC-astrocytes after oAβ stimulation[1].
NLRP3-IN-96 binds to human recombinant NLRP3 with a KD of 556 nM[1].
NLRP3-IN-96 (10 μM; 30 min) blocks the binding of [18F]-22 to NLRP3 in wild-type mouse brain slices, supporting its selective binding to NLRP3[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:AD-derived hiPSC-microglia
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Concentration:1 μM; 10 μM
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Incubation Time:24 h
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Result:oAβ elevated NLRP3 expression; 10 μM NLRP3-IN-96 decreased NLRP3 expression by 2.5-fold.
Did not significantly alter oAβ GFP fluorescent intensity but showed a trending increase in oAβ phagocytosis.
With TNFα/IFNγ stimulation, NLRP3-IN-96 reduced NLRP3 expression, and a lower concentration also comparably suppressed NLRP3 expression.
Microglia morphology changed with longer projections upon NLRP3-IN-96 exposure.
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Cell Line:hiPSC-astrocytes
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Concentration:1 μM
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Incubation Time:24 h
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Result:Decreased NLRP3 expression in hiPSC-astrocytes upon oAβ stimulation.
Parmacokinetics
In Vivo
NLRP3-IN-96 (10-20 mg/kg; intraperitoneal injection; once daily; starting from postoperative day 21) alleviates CCI-induced neuropathic pain in mice and inhibits hippocampal inflammatory cytokines[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6[1]
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Dosage:5 mg/kg
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Administration:i.p.; single administration
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Result:Suppressed serum IL-1β.
Plasma TNF-α was decreased.
IL-6 level was not changed.
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Animal Model:C57BL/6 (male)[1]
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Dosage:10 mg/kg and 20 mg/kg
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Administration:i.p.; once daily; beginning on postoperative day 21
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Result:Compound 22 at both 10 mg/kg and 20 mg/kg increased mechanical withdrawal threshold and thermal withdrawal latency.
The 20 mg/kg dose appeared to provide a better analgesic effect.
In CCI mice, compound 22 at 20 mg/kg suppressed hippocampal IL-1β and TNF-α.
Chemical Information
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CAS No. 3113161-60-4
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Molecular Weight 444.93
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Formula C23H26ClFN4O2
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SMILES
CCCOC1=C(CN2N=NC(C(N(C(C)C)CC3=CC=C(F)C=C3)=O)=C2)C=C(Cl)C=C1
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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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RNA extraction experimental
By lysing cells, releasing RNA, and removing impurities such as proteins and DNA, high-purity RNA products are finally obtained. The commonly used traditional method is the guanidine isothiocyanate/phenol/chloroform method (Trizol), which is suitable for a variety of animal materials including animal tissues, microorganisms, cultured cells, etc., and most plant materials.
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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)