MCC950 - NLRP3 Inhibitor

InvitroFit™ Inflammasome inhibitor

ABOUT

NLRP3 inflammasome inhibitor

MCC950 is a potent and specific inhibitor of the NLRP3 (NOD-like receptor pyrin domain-containing protein 3, cryopyrin, or NALP3) inflammasome [1,2]. The multiprotein NLRP3 inflammasome complex is a key player in innate immunity. It participates in the production of the pro-inflammatory cytokines, interleukin-1β (IL-1β) and IL-18, as well as leading to alarmin secretion and pyroptosis, a form of immunogenic cell death.

More details More details

 

Mode of action:

MCC950 blocks the release of IL‑1β induced by NLRP3 activators, such as nigericin, ATP, and MSU crystals [3,4]. It inhibits the NLRP3 inflammasome by directly targeting the NLRP3 NATCH domain and interfering with the Walker B motif function thus preventing NLRP3 conformational change and oligomerization [1,2]. In research models of inflammation, such as cryopyrin-associated periodic syndromes (CAPS) and myocardial infarction, MCC950 effectively inhibited NLRP3-induced IL-1β production [3-5]. Importantly, MCC950 is a specific inhibitor of the NLRP3 inflammasome.  It displays no effect on the AIM2, NLRC4, or NLRP1 inflammasomes [4].

Key features:

  • A potent and specific inhibitor of the NLRP3 inflammasome
  • InvitroFit™ grade: each lot is highly pure (≥98%) and functionally tested

 

More detailsRead our review on the NLRP3 inflammasome.

More detailsDownload our Practical guide on Inflammasomes.

 

References:

1. Tapia-Abellán A. et al., 2019. MCC950 closes the active conformation of NLRP3 to an inactive state. Nature Chemical Biology. 15(6):560-4.
2. Coll R.C. et al., 2019. MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition. Nature Chemical Biology. 15(6):556-9.
3. Guo H. et al., 2015. Inflammasomes: mechanism of action, role in disease, and therapeutics. Nat Med. 21(7):677-87.
4. Coll RC. et al., 2015. A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nature Med 21(3), 248-255.
5. van Hout GP. et al., 2016. The selective NLRP3-inflammasome inhibitor MCC950 reduces infarct size and preserves cardiac function in a pig model of myocardial infarction. Eur Heart J. ehw247.

All products are for research use only, and not for human or veterinary use.

InvitroFit™

InvitroFit™ is a high-quality standard specifically adapted for in vitro studies of inhibitors. InvitroFit™ products are highly pure (≥95%) and guaranteed free of bacterial contamination, as confirmed using HEK Blue™ TLR2 and HEK Blue™ TLR4 cellular assays. Each lot is rigorously tested for functional activity using validated (or proprietary) cellular models. This grade ensures reliability and reproducibility for your research applications.

SPECIFICATIONS

Specifications

CAS number
210826-40-7
Chemical formula

C20H24N2O5S

Molecular weight
404.48 g/mol
Purity
≥ 98% (UHPLC)
Solubility

10 mg/ml in DMSO

Working concentration

300 nM (121.34 ng/ml) to 10 μM (4.04 μg/ml) for cell culture assays

Endotoxin

Negative (tested using EndotoxDetect™ assay)

Tested applications

In vitro Inflammasome cellular assays

Quality control

Each lot is functionally tested and validated using cellular assays.

CONTENTS

Contents

  • Product: 
    MCC950
  • Cat code: 
    inh-mcc
  • Quantity: 
    10 mg
Notes:

MCC950 is provided as a translucent film.

Shipping & Storage

  • Shipping method:  Room temperature
  • Storage:

    • -20°C
    Stability: The reconstituted product is stable up to 6 months at -20 °C.

    Caution:

    • Avoid repeated freeze-thaw cycles

Details

The NLRP3 Inflammasome:

The NLRP3 inflammasome is an innate immune sensor that is activated by a two-step process; a first signal (‘priming’) provided mainly by bacterial components or endogenous cytokines involves NF-κB induction, while the second signal provided by a wide array of stimuli including microbial toxins, endogenous molecules or crystalline substances and leads to inflammasome assembly and activation [1, 2].  This triggers inflammasome multimerization and caspase-1 activation with the subsequent cleavage of interleukin-1β (IL-1β)/IL-18 and the pore-forming protein Gasdermin D (GSDMD) into their active forms. Additionally, the activation of the inflammasome also leads to alarmin secretion and pyroptosis, a form of immunogenic cell death.

 

1. Swanson K.V. et al., 2019. The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat. Rev. Immunol. 19:477.
2. Groslambert M. & Py B. 2018. Spotlight on the NLRP3 inflammasome pathway. J. Inflamm. Res. 11:359.

 

Chemical structure of MCC950:

MCC950 chemical structure

DOCUMENTS

Documents

MCC950

Technical Data Sheet

Safety Data Sheet

Validation Data Sheet

Certificate of analysis

Need a CoA ?

CUSTOMER SERVICE & TECHNICAL SUPPORT

Question about this product ?