MCC950 sodium salt (CP-456773)

生物活性

MCC950 (CP-456773) sodium salt 是一种有效的、选择性的NLRP3和细胞焦亡 (pyroptosis) 抑制剂，在骨髓来源的巨噬细胞和人类单核细胞衍生的巨噬细胞中，抑制经典和非经典NLRP3激活，IC50分别为7.5和8.1 nM。MCC950特异性抑制NLRP3的激活，不抑制AIM2，NLRC4或NLRP1这些炎症小体。

MCC950还能剂量依赖性地抑制IL-1β的分泌，但不能抑制TNF-α的分泌。MCC950能特异性地阻断caspase-11引导的NLR3激活和非经典途径刺激下的IL-1β分泌。MCC950即使在10μM的浓度下，也不会抑制NLRC4刺激的IL-1β和TNF-α分泌（由鼠伤寒沙门氏菌激活）。

使用AbMole产品发表的文献

• 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

• 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

• 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

• 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

• 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

• BMC Neurosci. 2022 Nov 27;23(1):70.

  NLRP3 inflammasome regulates astrocyte transformation in brain injury induced by chronic intermittent hypoxia

• 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

• Front Pharmacol. 2021 May 31;12:599393.

  Histamine H 3 Receptor Signaling Regulates the NLRP3 Inflammasome Activation in C2C12 Myocyte During Myogenic Differentiation

• Cell Rep. 2020 May 19;31(7):107667.

  hGBP1 Coordinates Chlamydia Restriction and Inflammasome Activation through Sequential GTP Hydrolysis

• 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

• Journal of Immunology Research. 2018 Sep 30.

  Sevoflurane Inhibits the Th2 Response and NLRP3 Expression in Murine Allergic Airway Inflammation.

产品使用成果展示

	数据来源	Journal of Immunology Research (2018). Figure 6. MCC950 (Abmole Bioscience, USA)
	方法	i.p.
	细胞系/动物模型	mice
	浓度	10 mg/kg
	处理时间	24 h
	实验结果	More interestingly, we found that sevoflurane abolished the OVA-induced expression of NLRP3, which is similar to that observed in MCC950-treated allergic mice.

	数据来源	Journal of Immunology Research (2018). Figure 5. MCC950 (Abmole Bioscience, USA)
	方法	i.p.
	细胞系/动物模型	mice
	浓度	10 mg/kg
	处理时间	24 h
	实验结果	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

	数据来源	Journal of Immunology Research (2018). Figure 4. MCC950 (Abmole Bioscience, USA)
	方法	i.p.
	细胞系/动物模型	mice
	浓度	10 mg/kg
	处理时间	24 h
	实验结果	Sevoflurane or MCC950 treatment resulted in a marked reduction in goblet cell hyperplasia (Figures 4(a)-4(f))

	数据来源	Journal of Immunology Research (2018). Figure 3. MCC950 (Abmole Bioscience, USA)
	方法	i.p.
	细胞系/动物模型	mice
	浓度	10 mg/kg
	处理时间	24 h
	实验结果	Treatment with sevoflurane or MCC950 produced a profound reduction in the total numbers and differential counts of inflammatory cells in BALF

	数据来源	Journal of Immunology Research (2018). Figure 2. MCC950 (Abmole Bioscience, USA)
	方法	i.p.
	细胞系/动物模型	mice
	浓度	10 mg/kg
	处理时间	24 h
	实验结果	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)).

	数据来源	Neural Plast (2018). Figure 3. MCC950
	方法	i.p
	细胞系/动物模型	mice
	浓度	50 mg/kg
	处理时间	24 hr
	实验结果	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

化学性质

分子量	426.46
分子式	C20H23N2NaO5S
CAS号	256373-96-3
溶解性（25°C）	Water 30 mg/mL DMSO 80 mg/mL
储存条件	粉末型式       -20°C   3年；4°C   2年 溶于溶剂       -80°C   6个月；-20°C   1个月
运输方式	冰袋运输，根据产品的不同，可能会有相应调整。

储备液配制

*下述溶液配置方法仅为基于分子量计算出的理论值。不同产品在配置溶液前，需考虑其在不同溶剂中的溶解度限制。

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	2.3449 mL	11.7244 mL	23.4489 mL
5 mM	0.469 mL	2.3449 mL	4.6898 mL
10 mM	0.2345 mL	1.1724 mL	2.3449 mL

不同实验动物依据体表面积的等效剂量转换表（参考来源于公开文献）

	小鼠	大鼠	兔	豚鼠	仓鼠	狗
重量 (kg)	0.02	0.15	1.8	0.4	0.08	10
体表面积 (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km 系数	3	6	12	8	5	20

动物 A (mg/kg) = 动物 B (mg/kg) ×	动物 B的Km系数
	动物 A的Km系数

例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的K_m系数（3），再除以大鼠的K_m系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。

参考文献

[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