MCC950 210826-40-7 98% White to Off-White Solid Selective NLRP3 Inflammasome Inhibitor for Research

1. Product Overview

MCC950 (CAS 210826-40-7), also known as CP-456773 or CRID3, is a highly potent, selective, and cell-permeable small-molecule inhibitor of the NLRP3 (NOD-like receptor family pyrin domain-containing protein 3) inflammasome. It binds directly to the Walker B motif in the NACHT domain of NLRP3, preventing ATP hydrolysis and thereby blocking NLRP3 inflammasome assembly and caspase-1 activation. MCC950 inhibits IL-1β secretion with IC₅₀ values of ~7.5 nM in mouse bone marrow-derived macrophages (BMDMs) and ~8.1 nM in human monocyte-derived macrophages (HMDMs), without affecting AIM2, NLRC4, or NLRP1 inflammasomes.

2. Key Features and Benefits

• Exceptional Selectivity: Specifically targets NLRP3; does not inhibit NLRC4, NLRP1, AIM2 inflammasomes or TLR-induced NF-κB activation, even at 10 µM.

• Sub-nanomolar Potency: Blocks both canonical (ATP/nigericin) and non-canonical (LPS + caspase-11) NLRP3 activation pathways at low nanomolar concentrations.

• Well-Characterized In Vivo: Demonstrated efficacy in multiple disease models including experimental autoimmune encephalomyelitis (EAE), Alzheimer's disease models, and gout/crystal-induced inflammation.

• Dual Solubility: Soluble in both DMSO (up to ~40 mg/mL) and aqueous buffers (up to ~30 mg/mL as sodium salt or with mild base), facilitating both cell-based and in vivo studies.

• Published Gold Standard: The most widely cited small-molecule NLRP3 inhibitor, with over 1000 peer-reviewed citations validating its mechanism and applications.

3. Major Applications

• Inflammasome Research: Used to dissect NLRP3-specific versus NLRP1/AIM2/NLRC4 inflammasome signaling in macrophages, dendritic cells, and microglia.

• Autoinflammatory & Autoimmune Disease Models: Applied in studies of cryopyrin-associated periodic syndromes (CAPS), rheumatoid arthritis, type 2 diabetes, atherosclerosis, and multiple sclerosis (EAE model).

• Neuroinflammation: Investigated for NLRP3-mediated neuroinflammation in Alzheimer's, Parkinson's, and ischemic stroke models.

• Metabolic Inflammation: Used to probe the link between metabolic stress (palmitate, glucose) and NLRP3 activation in adipose tissue and pancreatic islets.

• Gout & Crystal-Induced Inflammation: Employed to block MSU (monosodium urate) crystal- or CPPD crystal-induced IL-1β release in vitro and in vivo.

4. Technical Specifications

5. Storage and Handling

• Powder Storage: Store sealed vial at -20°C (or -80°C for long-term), protected from light in a desiccated environment. Stable for at least 24 months from date of manufacture.

• Stock Solution: Dissolve in anhydrous DMSO to 10–20 mM (4–8 mg/mL). Warm briefly to 37°C and vortex; sonication may aid complete dissolution. Protect from light.

• Working Dilution: Dilute into cell culture medium immediately before use. Final DMSO in assay should not exceed 0.1% (v/v). For aqueous work, a small amount of NaOH or NaHCO₃ can be used to enhance water solubility.

• Freeze-Thaw: Aliquot DMSO stocks upon preparation. Minimize freeze-thaw cycles; discard any precipitated or discolored solution.

6. Safety Summary

• GHS Classification: GHS07 – Warning

• Hazard Statements: H303 (May be harmful if swallowed); H315 (Causes skin irritation); H319 (Causes serious eye irritation); H335 (May cause respiratory irritation).

• Precautionary Statements: P261 (Avoid breathing dust/mist); P264 (Wash after handling); P280 (Wear protective gloves/eye protection); P302+P352 (If on skin: wash with soap and water); P305+P351+P338 (If in eyes: rinse with water several minutes; remove contact lenses if present); P337+P313 (If eye irritation persists: seek medical advice).

• Intended Use: For laboratory research and development ONLY. Not for human or veterinary therapeutic, diagnostic, or food use. Handle as a bioactive compound.

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