MCC950 sodium salt (CP-456773)

Biological Activity

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 (CP-456773) sodium salt inhibits interleukin 1β (IL-1β) secretion and caspase 1 processing.

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.

Product Citations

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  Engineering. 2024 Jun.

  Activation of the Macrophage-Associated Inflammasome Exacerbates Myocardial Fibrosis Through the 15-HETE-Mediated Pathway in Acute Myocardial Infarction
  MCC950 sodium salt (CP-456773) purchased from AbMole

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  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 sodium salt (CP-456773) purchased from AbMole

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  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 sodium salt (CP-456773) purchased from AbMole

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  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 sodium salt (CP-456773) purchased from AbMole

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  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 sodium salt (CP-456773) purchased from AbMole

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  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 sodium salt (CP-456773) purchased from AbMole

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  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 sodium salt (CP-456773) purchased from AbMole

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  BMC Neurosci. 2022 Nov 27;23(1):70.

  NLRP3 inflammasome regulates astrocyte transformation in brain injury induced by chronic intermittent hypoxia
  MCC950 sodium salt (CP-456773) purchased from AbMole

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  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 sodium salt (CP-456773) purchased from AbMole

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  Front Pharmacol. 2021 May 31;12:599393.

  Histamine H 3 Receptor Signaling Regulates the NLRP3 Inflammasome Activation in C2C12 Myocyte During Myogenic Differentiation
  MCC950 sodium salt (CP-456773) purchased from AbMole

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  Cell Rep. 2020 May 19;31(7):107667.

  hGBP1 Coordinates Chlamydia Restriction and Inflammasome Activation through Sequential GTP Hydrolysis
  MCC950 sodium salt (CP-456773) purchased from AbMole

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  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 sodium salt (CP-456773) purchased from AbMole

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  Journal of Immunology Research. 2018 Sep 30.

  Sevoflurane Inhibits the Th2 Response and NLRP3 Expression in Murine Allergic Airway Inflammation.
  MCC950 sodium salt (CP-456773) purchased from AbMole

Customer Product Validations & Biological Datas

	Source	Journal of Immunology Research (2018). Figure 6. MCC950 (Abmole Bioscience, USA)
	Method	i.p.
	Cell Lines	mice
	Concentrations	10 mg/kg
	Incubation Time	24 h
	Results	More interestingly, we found that sevoflurane abolished the OVA-induced expression of NLRP3, which is similar to that observed in MCC950-treated allergic mice.

	Source	Journal of Immunology Research (2018). Figure 5. MCC950 (Abmole Bioscience, USA)
	Method	i.p.
	Cell Lines	mice
	Concentrations	10 mg/kg
	Incubation Time	24 h
	Results	As expected, OVA challenge significantly increased the production of serum IgE compared with that of the control groups. Sevoflurane or MCC950 treatment significantly decreased OVA-induced IgE levels, although these levels remained higher than those in the control mice

	Source	Journal of Immunology Research (2018). Figure 4. MCC950 (Abmole Bioscience, USA)
	Method	i.p.
	Cell Lines	mice
	Concentrations	10 mg/kg
	Incubation Time	24 h
	Results	Sevoflurane or MCC950 treatment resulted in a marked reduction in goblet cell hyperplasia (Figures 4(a)-4(f))

	Source	Journal of Immunology Research (2018). Figure 3. MCC950 (Abmole Bioscience, USA)
	Method	i.p.
	Cell Lines	mice
	Concentrations	10 mg/kg
	Incubation Time	24 h
	Results	Treatment with sevoflurane or MCC950 produced a profound reduction in the total numbers and differential counts of inflammatory cells in BALF

	Source	Journal of Immunology Research (2018). Figure 2. MCC950 (Abmole Bioscience, USA)
	Method	i.p.
	Cell Lines	mice
	Concentrations	10 mg/kg
	Incubation Time	24 h
	Results	OVA challenge significantly increased the inflammatory cells concentrated near the airways (Figure 2(c)), while sevoflurane or MCC950 treatment resulted in a marked decrease in inflammatory cell infiltration (Figures 2(d)-2(f)).

	Source	Neural Plast (2018). Figure 3. MCC950
	Method	i.p
	Cell Lines	mice
	Concentrations	50 mg/kg
	Incubation Time	24 hr
	Results	When compared with the vehicle group, MCC950, the NLRP3 inhibitor significantly reduced the neurological deficit score 24 hr after cerebral ischemia reperfusion in diabetic mice

Chemical Information

Molecular Weight	426.46
Formula	C20H23N2NaO5S
CAS Number	256373-96-3
Solubility (25°C)	Water 30 mg/mL DMSO 80 mg/mL
Storage	Powder          -20°C   3 years ;  4°C   2 years In solvent       -80°C   6 months ;  -20°C   1 month

References

[1] Yifan Wang, et al. Biomed Res Int. Overexpression of Limb Bud and Heart Alleviates Sepsis-Induced Acute Lung Injury via Inhibiting the NLRP3 Inflammasome

[2] Hui Yin, et al. Anat Rec (Hoboken). Resibufogenin suppresses growth and metastasis through inducing caspase-1-dependent pyroptosis via ROS-mediated NF-κB suppression in non-small cell lung cancer

[3] Qinyu Wang, et al. Br J Pharmacol. Naringenin attenuates non-alcoholic fatty liver disease by down-regulating the NLRP3/NF-κB pathway in mice

[4] Cong-Fa Huang, et al. J Exp Clin Cancer Res. NLRP3 inflammasome activation promotes inflammation-induced carcinogenesis in head and neck squamous cell carcinoma

[5] Dempsey C, et al. Brain Behav Immun. Inhibiting the NLRP3 inflammasome with MCC950 promotes non-phlogistic clearance of amyloid-β and cognitive function in APP/PS1 mice.

[6] Salla M, et al. ACS Med Chem Lett. dentification, Synthesis, and Biological Evaluation of the Major Human Metabolite of NLRP3 Inflammasome Inhibitor MCC950.

[7] Rebecca C Coll, et al. Nat Med. A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases