NLRP3 Inhibitor, MCC950

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 (<15% inhibition at 10 µM) & hERG (IC50 >30 µM). It has demonstrated effectiveness against metabolic diseases, autoimmune diseases, cardiovascular diseases, and other conditions.

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.

Cell permeable: yes

Primary Target
NLRP3

Reversible: yes

Packaged under inert gas

Toxicity: Standard Handling (A)

Supplied as a sodium salt.

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

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.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany