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5.38120

NLRP3 Inhibitor, MCC950

Name: NLRP3 Inhibitor, MCC950
Brand: MM

Synonym(s):

NLRP3 Inhibitor, MCC950, N-(1,2,3,5,6,7-Hexahydro- s-indacen-4-ylcarbamoyl)-4-(2-hydroxy-2-propanyl)-2-furansulfonamide, Sodium, MCC-950, MCC950, Cytokine Release Inhibitory Drug 3, CRID 3, CP-456,773

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About This Item

Empirical Formula (Hill Notation):

C₂₀H₂₃N₂O₅S · Na

CAS Number:

256373-96-3

Molecular Weight:

426.46

MDL number:

MFCD30478884

UNSPSC Code:

51111800

NACRES:

NA.77

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Properties

assay

≥97% (HPLC)

Quality Segment

100

form

powder

manufacturer/tradename

Calbiochem^®

storage condition

OK to freeze, desiccated (hygroscopic), protect from light

color

white

solubility

water: 1 mg/mL, DMSO: 50 mg/mL

storage temp.

−20°C

SMILES string

[Na+].[S](=O)(=O)(N=C(Nc2c3c(cc4c2CCC4)CCC3)[O-])c1[o]cc(c1)C(O)(C)C

InChI

1S/C20H24N2O5S.Na/c1-20(2,24)14-10-17(27-11-14)28(25,26)22-19(23)21-18-15-7-3-5-12(15)9-13-6-4-8-16(13)18;/h9-11,24H,3-8H2,1-2H3,(H2,21,22,23);/q;+1/p-1

InChI key

LFQQNXFKPNZRFT-UHFFFAOYSA-M

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 (<15% inhibition at 10 µM) & hERG (IC50 >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)

Storage Class

11 - Combustible Solids

wgk

WGK 3

flash_point_f

Not applicable

flash_point_c