NLRP3 INHIBITOR MCC950

General description

A cell-permeable, bioavailable, non-toxic sulfonylurea derived compound that selectively interacts with 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 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 inhibit NLRC4, AIM2, TLR signaling or NLRP3 priming. Effectively suppresses T cell responses and IL-1β & IL-6 secretion, and 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 attractive PK profile with desirable microsomal stability and minimal liability towards CYP450 isozymes (<15% inhibition at 10 µM) & hERG (IC₅₀ >30 µM).

A cell-permeable, bioavailable, non-toxic sulfonylurea derived compound that selectively interacts with 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 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 inhibit NLRC4, AIM2, TLR signaling or NLRP3 priming. Effectively suppresses T cell responses and IL-1β & IL-6 secretion, and 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 attractive PK profile with desirable microsomal stability and minimal liability towards CYP450 isozymes (<15% inhibition at 10 µM) & hERG (IC₅₀ >30 µM).

Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
NLRP3

Reversible: yes

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Physical form

Supplied as a sodium salt.

Reconstitution

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

Other Notes

Coll, R.C., et al. 2015. Nat. Med.21, 248.
Coll, R.C. and O′Neill, L.A.J. 2011. PLoS ONE.6, e29539.
Laliberte, R.E., et al. 2003. J. Biol. Chem.278, 16567.
Perregaux, D.G., et al. 2001. J. Pharmacol. Exp. Ther.299, 187.

Legal Information

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