NF-κB and NLRP3 inflammasome inhibitor - BAY 11-7082

NF-κB inhibitor - NLRP3 inhibitor

Inhibitory activity of BAY 11-7082

BAY 11-7082 was first described as an irreversible inhibitor of the NF-κB pathway [1]. A number of reports have since shown that BAY 11-7082 has multiple targets, including the NLRP3 (NOD-like receptor pyrin domain-containing protein 3, cryopyrin, or NALP3) inflammasome sensor [2].  The multiprotein NLRP3 inflammasome complex is a key player in innate immunity.

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Modes of action:

Inhibition of NF-κB translocation into the nucleus: BAY11-7082 inhibits the phosphorylation of IκB-α, which is essential for the release of NF-κB from the cytosolic IκB-α/ NF-κB complex [1]. The transcription factor NF-κB regulates multiple aspects of innate and adaptive immune functions and serves as a pivotal mediator of inflammatory responses.

Inhibition of inflammasome responses: BAY 11-7082 may inhibit the inflammasome responses indirectly by preventing the nuclear translocation of  NF-κB at the priming step. Moreover, BAY 11-7082 has been shown to exhibit direct inhibitory functions on the NLRP3 inflammasome by blocking the sensor's ATPase activity [2].
 

Key features:

• Potent inhibitor of NF-κB and the NLRP3 inflammasome
• Does not inhibit the NLRP1 inflammasome
• InvitroFit™ grade: each lot is highly pure (≥95%) and functionally tested

Read our review on the NLRP3 inflammasome.

Download our Practical guide on Inflammasomes.

References

1. Pierce JW. et al., 1997. Novel Inhibitors of Cytokine-induced Ikappa Balpha Phosphorylation and Endothelial Cell Adhesion Molecule Expression Show Anti-inflammatory Effects in Vivo.J. Biol. Chem., 272: 21096.
2. Juliana C. et al, 2010. Anti-inflammatory Compounds Parthenolide and Bay11-7082 Are Direct Inhibitors of the Inflammasome. J. Biol Chem. 285(13): 9792–9802. 

Figures

Bay11-7082 inhibits the NLRP3 inflammasome response in a dose-dependent manner.
THP1-Null2 cells were primed with LPS-EK (1 μg/ml) for 3 h and then stimulated with MSU (150 µg/ml) and increasing concentrations of Bay11-7082. After overnight incubation, IL-1β secretion was analyzed by adding 50 µl of supernatant from treated THP1-Null2 cells to HEK‑Blue™ IL‑1β cells. IL‑1β‑induced activation of NF-κB was assessed by measuring the levels of SEAP in the supernatant of HEK-Blue™ IL-1β cells using QUANTI‑Blue™ Solution, a SEAP detection reagent, and by reading the optical density (OD) at 655 nm. Data are shown as percentage (%) inhibition.

Specifications

Working concentration: 1-10 μM

CAS number: 19542-67-7

Molecular weight: 207.25 g/mol

Solubility: 25 mg/ml in DMSO and 15 mg/ml in ethanol

Quality control:

• Purity: ≥95% (UHPLC)
• The inhibitory activity of the product has been validated using cellular assays.
• The absence of bacterial contamination (e.g. lipoproteins and endotoxins) is confirmed using HEK-Blue™ TLR2 and HEK-Blue™ TLR4 cells.

Contents

BAY 11-7082 is available in two quantities:

• tlrl-b82: 10 mg
• tlrl-b82-5: 5 x 10 mg

BAY 11-7082 is shipped at room temperature.

 Upon receipt, store at -20°C.

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 Bay 11-7082: