The NOD-like receptor family protein NLRP3 is an intracellular signaling molecular that forms a complex termed inflammasome with other proteins during inflammatory process, which promotes the release of proinflammatory cytokines, such as IL-1β and IL-18. MCC950 sodium is a potent and selective inhibitor of NLRP3. It inhibits the release of IL-1β with IC50 values of 7.5 nM in mouse bone marrow derived macrophages (BMDM) and 8.1 nM in human monocyte derived macrophages. The amount of caspase-1 p10 was reduced in the supernatants of BMDM and human peripheral blood mononuclear cells (PBMC) after the treatment of 10 and 50 nM MCC950. In BMDM stimulated by LPS and nigericin, MCC950 from 0.1 – 10 μM potently inhibited the release of IL-1α and lactate dehydrogenase. Pre-treatment of 0.01 – 1 μM MCC950 before the transfection of LPS dose-dependently inhibited the release of IL-β in BMDM. The expression of ASC complex was blocked by 10 and 50 nM MCC950 in LPS- and nigericin-treated BMDM. The amount of ASC-cerulean cells containing an ASC speck was dose-dependently decreased by the pre-treatment of 0.05 – 10 μM MCC950. Pre-treatment of MCC950 (50 mg/kg) one hour before the intraperitoneal injection of LPS in C57BL/6 mice decreased the serum concentration of IL-1β and IL-6. Treatment of MCC950 (10 mg/kg, i.p.) postponed the onset and attenuated the severity of EAE in C57BL/6 mice. MWS mice that received i.p. administration of MCC950 (20 mg/kg) showed increased body weight, elevated survival rate and reduced concentration of circulating IL-18[1].
作用机制
MCC950 sodium might have an inhibitory effect on a critical step in NLRP3 activation at post-translational level[1].
MCC950 sodium 细胞实验
Cell Line
Concentration
Treated Time
Description
References
B-lymphocytes
100 µM
24 h
Inhibition of NLRP3 inflammasome, reducing IL-1β secretion
Front Immunol. 2017 Nov 9;8:1504.
primary PBMC
1 μM
24 h
Tested the effect of MCC950 in LPS-stimulated PBMC, results showed MCC950 had no preventive effect on cell death
Cell Death Differ. 2022 Aug;29(8):1486-1499.
THP1 monocytic cells
1 μM
Tested the effect of MCC950 in THP1 cells, results showed MCC950 had no preventive effect on cell death
Cell Death Differ. 2022 Aug;29(8):1486-1499.
BV2 microglia
10 µM
30 min
To evaluate the effect of MCC950 on sevoflurane-induced inflammation in BV2 microglia. Results showed that MCC950 pretreatment significantly inhibited sevoflurane-induced NLRP3 inflammasome activation.
Int J Biol Sci. 2024 Mar 3;20(5):1927-1946.
PDL progenitor cells
10 μM
6 h
To investigate the regulation of force-induced pyroptosis in PDL progenitor cells, MCC950 partially suppressed the expression of pyroptosis-related proteins
Int J Oral Sci. 2024 Jan 15;16(1):3.
MCC950 sodium 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Orthodontic tooth movement model
Intraperitoneal injection
20 mg/kg
Every two days for 7 days
To investigate the influence of pyroptosis level on orthodontic tooth movement, MCC950 inhibited the expression of pyroptosis-related markers and reduced the tooth movement distance
Int J Oral Sci. 2024 Jan 15;16(1):3.
Mice
DSS-induced colitis model
Intraperitoneal injection
20 mg/kg
Once daily for 2 days
MCC950 significantly alleviated C. difficile-induced colitis, reducing neutrophil accumulation and inflammatory responses
Gut Microbes. 2023 Jan-Dec;15(1):2192478
Mice
Pml−/− mouse model
Intraperitoneal injection
20 mg/kg
Single injection
MCC950, as an NLRP3 inhibitor, was able to suppress NLRP3 activation in Pml?/? mice, thereby reducing IL-1β release.
Cell Death Differ. 2023 Feb;30(2):429-441
Mice
Dsg2mut/mut mice
Subcutaneous injection
5 mg/kg
Continuous for 4 weeks
Inhibition of NLRP3 inflammasome significantly alleviates right ventricular dilation and dysfunction
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