MCC950 sodium salt (CP-456773)

Biological Activity

MCC950 (CP-456773) sodium salt was found to act as a cytokine release inhibitory drug and inhibitor of the NLRP3 inflammasome. CP-456773 sodium salt inhibits interleukin 1β (IL-1β) secretion and caspase 1 processing.

Product Citations

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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

• 

  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

• 

  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

• 

  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

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

Chemical Information

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