Caspase-1 and inflammasome inhibitor – Parthenolide
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Caspase-1 and inflammasome inhibitor
Caspase-1 and inflammasome inhibitor
Parthenolide is a broad-spectrum inhibitor with numerous anti-inflammatory properties . Its targets include NF‑κB, caspase-1, and multiple inflammasomes [1, 2]. Inflammasomes are large intracellular multiprotein complexes that play a central role in innate immunity.
Mode of action
Parthenolide blocks the activity of the NLRP1, NLRP3, NLRC4 inflammasomes, but not the AIM2 inflammasome [2-4]. Mechanistically, it has been reported that parthenolide inhibits the IκB kinase function required for NF-κB activation , and alkylates the cysteine residues in caspase-1 and in the ATPase domain of NLRP3, thereby blocking their activity [1, 2].
- Caspase-1 and NF-κB inhibitor
- Inhibits the NLRP1, NLRP3, and NLRC4 inflammasomes
- Each lot is highly pure (≥95%) and functionally tested
1. Zahid A. et al., 2019. Pharmacological Inhibitors of the NLRP3 Inflammasome. Front Immunol. 2019. 10(2538).
2. Juliana C. et al., 2010. Anti-inflammatory compounds parthenolide and Bay 11-7082 are direct inhibitors of the inflammasome. J Biol Chem. 285(13):9792-802.
3. Coll R.C. & O’Neill L.A.J., 2011. The cytokine release inhibitory drug CRID3 targets ASC oligomerisation in the NLRP3 and AIM2 inflammasomes. PLoS One. 6(12): e29539.
4. Honda H. et al., 2014. Isoliquiritigenin is a potent inhibitor of NLRP3 inflammasome activation and diet-induced adipose tissue inflammation. J Leukoc Biol. 96(6): 1087-100.
5. Saadane A. et al., 2007. Parthenolide inhibits IκB kinase, NF-κB activation, and inflammatory response in cystic fibrosis cells and mice. Am J Respir Cell Mol Biol. 36(6):728-36.
Parthenolide 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 parthenolide. 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.
Solubility: 50 mg/ml (202 mM) in DMSO or ethanol
CAS number: 20554-84-1
Molecular weight: 248 g/mol
- Purity ≥95% (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.
- 50 mg Parthenolide (provided as a powder)
Parthenolide is shipped at room temperature.
Store at -20 °C.
Resuspended product is stable for at least 6 months when properly stored.
Avoid repeated freeze-thaw cycles.Back to the top
The inflammasomes are innate immune sensors that drive the activation of inflammatory caspases including caspase-1. They are 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. Numerous inflammasomes have been described among them the NLRP3 inflammasome has been best characterized .
1. Zheng, D. et al., 2020. Inflammasome activation and regulation: toward a better understanding of complex mechanisms. Cell Discov 6, 36.
Chemical structure of Parthenolide:
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