5.38120

NLRP3 Inhibitor, MCC950

• Szinonimák: 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
• Tapasztalati képlet (Hill-képlet): C₂₀H₂₃N₂O₅S · Na
• CAS-szám: 256373-96-3
• Molekulatömeg: 426.46
• UNSPSC kód: 51111800
• NACRES: NA.77

Tulajdonságok

• Teszt: ≥97% (HPLC)
• Minőségi szint: 100
• form: powder
• gyártó/kereskedő neve: Calbiochem^®
• tárolási körülmény: OK to freeze; desiccated (hygroscopic); protect from light
• szín: white
• oldhatóság: water: 1 mg/mL; DMSO: 50 mg/mL
• tárolási hőmérséklet: −20°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
• Nemzetközi kémiai azonosító kulcs: LFQQNXFKPNZRFT-UHFFFAOYSA-M

Leírás

Általános leírás

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.

Alkalmazás

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.

Biokémiai/fiziológiai hatások

Cell permeable: yes

Primary Target
NLRP3

Reversible: yes

Kiszerelés

Packaged under inert gas

Figyelmeztetés

Toxicity: Standard Handling (A)

Fizikai forma

Supplied as a sodium salt.

Feloldás

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

Egyéb megjegyzések

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.

Jogi információk

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

Biztonsági adatok

• Tárolási osztály kódja: 11 - Combustible Solids
• WGK: WGK 3
• Lobbanási pont (F): Not applicable
• Lobbanási pont (C): Not applicable