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In vitro: MCC950 (CP-456773) blocks canonical and non-canonical NLRP3 activation at nanomolar concentrations. MCC950 specifically inhibits NLRP3 but not AIM2, NLRC4 or NLRP1 activation. The effect of MCC950 on NLRP3 inflammasome activation is tested in mouse bone marrow derived macrophages (BMDM) and human monocyte derived macrophages (HMDM). The IC50 of MCC950 in BMDM is approximately 7.5 nM, while in HMDM it has a similar inhibitory capacity (IC50=8.1 nM). MCC950 also dose dependently inhibit IL-1β but not TNF-α secretion.MCC950 specifically blocks caspase-11-directed NLRP3 activation and IL-1β secretion upon stimulation of the non-canonical pathway. NLRC4-stimulated IL-1β and TNF-α secretion (as activated by Salmonella typhimurium) are not inhibited by MCC950 even at a concentration of 10 µM. MCC950 does not inhibit caspase-1 activation or IL-1β processing in response to S. typhimurium. The expression of pro-caspase-1 and pro-IL-1β in cell lysates is not substantially affected by MCC950 treatment.
In vivo: MCC950 (CP-456773) reduces Interleukin-1p (IL-1β) production and attenuates the severity of experimental autoimmune encephalomyelitis (EAE), a disease model of multiple sclerosis. Pre-treatment with MCC950 reduces serum concentrations of IL-1β and IL-6 while it does not considerably decrease the amount of TNF-α. Treatment of mice with MCC950 delays the onset and reduced the severity of EAE. Intracellular cytokine staining and FACS analysis of brain mononuclear cells from mice sacrificed on day 22 shows modestly reduced frequencies of IL-17 and IFN-γ producing CD3+ T cells in MCC950 treated mice in comparison with PBS-treated mice. IFN-γ and particularly IL-17 producing cell numbers are also reduced in both the CD4+ and γδ+ sub-populations of CD3+ T cells.
Int J Mol Sci. 2026 Jan 15; .
Luteolin Enhances Endothelial Barrier Function and Attenuates Myocardial Ischemia–Reperfusion Injury via FOXP1-NLRP3 Pathway
MCC950 purchased from AbMole
Phytochem Anal. 2026 Jan 20; .
Danqi Pill (DQP) Attenuates OGD‐Induced Injury in HUVECs via SHP2‐ROS‐NLRP3 Axis
MCC950 purchased from AbMole
Acta Pharm Sin B. 2025 Apr 10.
An anti-complement homogeneous polysaccharide from Houttuynia cordata ameliorates acute pneumonia with H1N1 and MRSA coinfection through rectifying Treg/Th17 imbalance in the gut–lung axis and NLRP3 inflammasome activation
MCC950 purchased from AbMole
J Ethnopharmacol. 2025 Aug 26; .
Qingqiao polyphenols improve DSS induced ulcerative colitis in mice by inhibiting NLRP3/AIM2 inflammasome mediated pyroptosis
MCC950 purchased from AbMole
Engineering. 2024 Jun.
Activation of the Macrophage-Associated Inflammasome Exacerbates Myocardial Fibrosis Through the 15-HETE-Mediated Pathway in Acute Myocardial Infarction
MCC950 purchased from AbMole
Pesticide Biochemistry and Physiology. 2024 Apr 27.
In vitro and in silico analyses reveal the toxicity of metolachlor to grass carp hepatocytes and the antagonism of melatonin
MCC950 purchased from AbMole
Biomed J. 2023 Feb 7;S2319-4170(23)00004-5.
Inhibition of NLRP3 attenuates sodium dextran sulfate-induced inflammatory bowel disease through gut microbiota regulation
MCC950 purchased from AbMole
Chin J Nat Med. 2023 Sep 6;21(10): 759-774.
Paeonol reduces microbial metabolite α-hydroxyisobutyric acid to alleviate the ROS/TXNIP/NLRP3 pathway-mediated endothelial inflammation in atherosclerosis mice
MCC950 purchased from AbMole
J Hazard Mater. 2022 Oct 5;439:129502.
Polystyrene nanoparticle exposure supports ROS-NLRP3 axis-dependent DNA-NET to promote liver inflammation
MCC950 purchased from AbMole
J Neuroimmune Pharmacol. 2022 Dec;17(3-4):503-514.
Inhibition of Microglial NLRP3 with MCC950 Attenuates Microglial Morphology and NLRP3/Caspase-1/IL-1β Signaling In Stress-induced Mice
MCC950 purchased from AbMole
J Inflamm Res. 2022 Sep 13;15:5309-5326.
P2X7R-NEK7-NLRP3 Inflammasome Activation: A Novel Therapeutic Pathway of Qishen Granule in the Treatment of Acute Myocardial Ischemia
MCC950 purchased from AbMole
Front Cell Infect Microbiol. 2022 Aug 9;12:925435.
Outer membrane vesicles of Porphyromonas gingivalis trigger NLRP3 inflammasome and induce neuroinflammation, tau phosphorylation, and memory
MCC950 purchased from AbMole
BMC Neurosci. 2022 Nov 27;23(1):70.
NLRP3 inflammasome regulates astrocyte transformation in brain injury induced by chronic intermittent hypoxia
MCC950 purchased from AbMole
Experimental Lung Research. 2022 Apr-Aug;48(4-6):168-177.
Low tidal volume ventilation alleviates ventilator-induced lung injury by regulating the NLRP3 inflammasome
MCC950 purchased from AbMole
Mol Cell Toxicol. 2022 Jan 10;1-11.
Ferulic acid exhibits anti-inflammatory effects by inducing autophagy and blocking NLRP3 inflammasome activation
MCC950 purchased from AbMole
Front Pharmacol. 2021 May 31;12:599393.
Histamine H 3 Receptor Signaling Regulates the NLRP3 Inflammasome Activation in C2C12 Myocyte During Myogenic Differentiation
MCC950 purchased from AbMole
Cell Rep. 2020 May 19;31(7):107667.
hGBP1 Coordinates Chlamydia Restriction and Inflammasome Activation through Sequential GTP Hydrolysis
MCC950 purchased from AbMole
Neurochem Res. 2020 Sep;45(9):2020-2031.
MCC950 Inhibits NLRP3 Inflammasome and Alleviates Axonal Injures in Early Stages of Diffuse Axonal Injury in Rats
MCC950 purchased from AbMole
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Source | Cell Reports 2020 May. Figure 3. MCC950 (Abmole Bioscience, USA) |
| Method | C. trachomatis infection | |
| Cell Lines | Human primary monocyte-derived macrophages | |
| Concentrations | 300 nM | |
| Incubation Time | 1 h | |
| Results | MCC950 treatment largely abolished infection-induced IL-1b secretion and pyroptosis. |
| Cell Experiment | |
|---|---|
| Cell lines | BMDM cell |
| Preparation method | For non-canonical inflammasome activation cells are primed with 100 ng/mL Pam3CSK4 for 4 h, medium is removed and replaced with SFM containing DMSO or MCC950 and 2 µg/mL LPS is transfected using 0.25% FuGENE for 16 h. Supernatants are removed and analysed using ELISA kits. LDH release is measured using the CytoTox96 non-radioactive cytotoxicity assay. |
| Concentrations | 0.001-10 µM |
| Incubation time | 16 h |
| Animal Experiment | |
|---|---|
| Animal models | C57BL/6 mice |
| Formulation | dissolved in DMSO and diluted with PBS |
| Dosages | 10 mg/kg |
| Administration | i.p. |
| Molecular Weight | 404.48 |
| Formula | C20H24N2O5S |
| CAS Number | 210826-40-7 |
| Solubility (25°C) | 28 mg/mL in DMSO |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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Disulfiram (Tetraethylthiuram disulfide) is a specific inhibitor of aldehyde-dehydrogenase (ALDH1). Disulfiram is used in the study of chronic alcoholism, with acute sensitivity to alcohol, and is a potent copper ion-carrier that can be used in cuproptosis studies. |
| Polyphyllin-VI
Polyphyllin VI, an active saponin, has anticancer activity. Polyphyllin VI induces G2/M cell cycle arrest and induces apoptosis. Polyphyllin VI induces caspase-1-mediated pyroptosis by inducing ROS/NF-κB/NLRP3/GSDMD signaling axis in non-small cell lung cancer. |
| 2-Bromohexadecanoic acid
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| MCC950 sodium salt (CP-456773)
MCC950 (CP-456773) sodium salt is a potent, selective NLRP3 inhibitor with IC50s of 7.5 and 8.1 nM in BMDMs and HMDMs, respectively. MCC950 specifically inhibits NLRP3 but not AIM2, NLRC4 or NLRP1 activation. |
| CY-09
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