NLRP3 Inhibitor, MCC950-CAS 256373-96-3-Calbiochem

C₂₀H₂₃N₂O₅S · Na

426.46

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.

Cell permeable: yes
Primary Target
NLRP3
Reversible: yes

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.

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.

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

100

≥97% (HPLC)

powder

Calbiochem^®

OK to freeze
desiccated (hygroscopic)
protect from light

white

water: 1 mg/mL
DMSO: 50 mg/mL

−20℃

Packaged under inert gas

11 - Combustible Solids

WGK 3