Description
General description
MCC950 is an antagonist ofInterleukin-1 beta (IL-1β). It interacts with both the inactive as well as active forms of NOD-like receptor protein 3 (NLRP3) and targets the Walker B motif within the NLRP3 NACHT domain. A cell-permeable, bioavailable, non-toxic sulfonylurea-derived compound that selectively interacts with the NLRP3 inflammasome and prevents its activation in a reversible manner with no effect on NLRC4 and NLRP1. Dose-dependently reduces IL-1β production (IC50 = 7.5 & 8.1 nM in LPS & ATP-treated BMDMs & HMDMs, respectively) with minimal effect on IL-1α & TNF-α. Specifically, it blocks NLRP3-dependent pyroptotic cell death by inhibiting caspase-1 &-11 activation, IL-1β processing, and ASC oligomerization. Does neither block K⁺efflux, Ca²⁺ flux, or NLRP3-ASC interactions nor inhibits NLRC4, AIM2, TLR signaling, or NLRP3 priming. Effectively suppresses T cell responses and IL-1β& IL-6 secretion, reduces the severity of EAE, and rescues neonatal lethality in a mouse model of CAPS (10 mg/kg, i.p., q.d., & 20 mg/kg, i.p., every other day, respectively). Displays an attractive PK profile with desirable microsomal stability and minimal liability towards CYP450 isozymes (30 µM). It has demonstrated effectiveness against metabolic diseases, autoimmune diseases, cardiovascular diseases, and other conditions.
Application
MCC950 has been used in:
hemolysis-affected mice to study the involvement of the NLRP3 inflammasome in kidney function injury.
MCC950-mediated inflammasome inhibition assays.
testing synergistic effect of pharmacologic inhibition of NLRP3 inflammasome in combination with immune checkpoint inhibitors (ICI) immunotherapy in tumor-bearing animals.
studying the role of NLRP3 inflammasome in the development of endothelial dysfunction in early sepsis in mice.
Biochem/physiol Actions
Cell permeable: yes
Primary Target
NLRP3
Reversible: yes
Packaging
Packaged under inert gas
Physical form
Supplied as a sodium salt.
Preparation Note
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.
Other Notes
Pleasenote that the molecular weight for this compound is batch-specific due tovariable water content. Please refer to the vial label or the certificate ofanalysis for the batch-specific molecular weight. The molecular weight providedrepresents the baseline molecular weight without water.
Legal Information
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Disclaimer
Toxicity: Standard Handling (A)
