NLRP3 inflammasome inhibitor - Glybenclamide
|Glybenclamide||Unit size||Cat. code||Docs||Price|
NLRP3 inflammasome inhibitor - Proton pump inhibitor
NLRP3 inflammasome inhibitor
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.
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 . 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].
- 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.
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.
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.
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)
- Purity ≥ 98% (UHPLC).
- The inhibitory activity of the product has been validated in inflammasome cellular assays using THP1-Null2 and HEK-Blue™ IL-1β cells.
- The absence of bacterial contamination (e.g. lipoproteins and endotoxins) has been confirmed using HEK-Blue™ TLR2 and HEK‑Blue™ TLR4 cells.
- 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.
Avoid repeated freeze-thaw cycles.Back to the top
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:
Back to the top