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NLRP3 inflammasome inhibitor - Glybenclamide

Glybenclamide Unit size Cat. code Docs Price
NLRP3 inflammasome inhibitor - Proton pump inhibitor
1 g
tlrl-gly

NLRP3 inflammasome inhibitor

Inhibitory activity of Glybenclamide
Inhibitory activity of Glybenclamide

Glybenclamide, also known as glyburide, is an ATP-sensitive potassium channel inhibitor and an inhibitor of the NLRP3 (NOD-like receptor pyrin domain-containing protein 3, cryopyrin, or NALP3) inflammasome [1-3]. The NLRP3 inflammasome is a multiprotein complex that plays a key role in innate immunity by participating 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.

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Mode of action:

Specifically, glybenclamide inhibits NLRP3 inflammasome activation by inducing the closure of ATP-sensitive K+ channels, and thereby raising the intracellular K+ concentration. This inhibitor works downstream of the ATP receptor P2X7, and upstream of NLRP3 [1]. Of note, its inhibitory activity appears to be specific for the NLRP3 inflammasome as it does not impact NLRC4- or NLRP1-mediated responses [1, 2].

 

Key features:

  • Potent  inhibitor of the NLRP3 inflammasome
  • Potent inhibitor of the ATP-sensitive potassium channel
  • Each lot is highly pure (≥98%) and functionally tested

 

Read our review on the NLRP3 inflammasome.

Download our Practical guide on Inflammasomes.

 

References:

1. Zahid A. et al., 2019. Pharmacological Inhibitors of the NLRP3 Inflammasome. Front Immunol. 10:2538.
2. Lamkanfi M. et al., 2009. Glyburide inhibits the Cryopyrin/Nalp3 inflammasome. J. Cell Biol., 187: 61 - 70.
3. Dostert C. et al., 2009. Malarial hemozoin is a Nalp3 inflammasome activating danger signal. PLoS One. 4(8):e6510.

Figures

Glybenclamide dose-dependent inhibition of NLRP3 inflammasome response in monocytes
Glybenclamide dose-dependent inhibition of NLRP3 inflammasome response in monocytes

Glybenclamide inhibits the NLRP3 inflammasome response in a dose-dependent manner.
THP1‑Null2 cells, primed with LPS-EK (1 μg/ml for 3 h), were stimulated with MSU (150 µg/ml) and increasing concentrations of glybenclamide. 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 a percentage (%) inhibition of the maximal response for the ligand with no inhibitor.

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Specifications

Working concentration: 20-200 μg/ml

CAS Number: 10238-21-8

Molecular weight: 494 g/mol

Solubility: Soluble in DMSO (25 mg/ml) and ethanol (5 mg/ml)

Quality control:

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Contents

  • 1 g of Glybenclamide (glyburide) provided as a powder

Product is shipped at room temperature.

 Upon receipt, store at room temperature (15-25 °C).

Resuspended product is stable for at least 6 months when properly stored.

Alert Avoid repeated freeze-thaw cycles.

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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 Glybenclamide:

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