1,2,4-Trimethoxybenzene
Based on 1 Customer Validation
1,2,4-Trimethoxybenzene is an orally active NLRP3 selective inhibitor. 1,2,4-Trimethoxybenzene can markedly suppress Nigericin (HY-127019) or ATP (HY-B2176)-induced NLRP3 inflammasome activation, thus decreasing caspase-1 activation and IL-1β secretion. 1,2,4-Trimethoxybenzene specifically inhibits the activation of NLRP3 inflammasome without affecting absent in melanoma 2 (AIM2) inflammasome activation. 1,2,4-Trimethoxybenzene inhibits oligomerization of the apoptosis-associated speck-like protein containing a CARD (ASC) and protein-protein interaction between NLRP3 and ASC, thus blocking NLRP3 inflammasome assembly. 1,2,4-Trimethoxybenzene can be used for the study of experimental autoimmune encephalomyelitis (EAE), multiple sclerosis, and type 2 diabetes.
For research use only. We do not sell to patients.
- CAS No.: 135-77-3
- Formula: C9H12O3
- Molecular Weight:168.19
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Storage:
Store at room temperature 3 years.
In solvent -80°C, 2 years , -20°C, 1 year
All Caspase Isoforms
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Biological Activity
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NLRP3 |
Caspase-1 |
IL-1β |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HepG2 | IC50 |
>10 μM
Compound: 1
|
Cytotoxicity against human HepG2 cells assessed as cell growth inhibition after 72 hrs by alamar blue assay
Cytotoxicity against human HepG2 cells assessed as cell growth inhibition after 72 hrs by alamar blue assay
|
[PMID: 31403289] |
| HL-60 | IC50 |
>10 μM
Compound: 1
|
Cytotoxicity against human HL60 cells assessed as cell growth inhibition after 72 hrs by alamar blue assay
Cytotoxicity against human HL60 cells assessed as cell growth inhibition after 72 hrs by alamar blue assay
|
[PMID: 31403289] |
| MCF7 | IC50 |
>10 μM
Compound: 1
|
Cytotoxicity against human MCF7 cells assessed as cell growth inhibition after 72 hrs by alamar blue assay
Cytotoxicity against human MCF7 cells assessed as cell growth inhibition after 72 hrs by alamar blue assay
|
[PMID: 31403289] |
| MRC5 | IC50 |
>10 μM
Compound: 1
|
Cytotoxicity against human MRC5 cells assessed as cell growth inhibition after 72 hrs by alamar blue assay
Cytotoxicity against human MRC5 cells assessed as cell growth inhibition after 72 hrs by alamar blue assay
|
[PMID: 31403289] |
1,2,4-Trimethoxybenzene (0.5-1 mM, 1.5 h) significantly inhibits Nigericin (HY-127019) and Lipopolysaccharides (HY-D1056) (LPS)-induced NLRP3 inflammasome activation in immortalized murine bone marrow-derived macrophages (iBMDMs), manifested as reduced caspase-1 (Casp-1) cleavage and IL-1β secretion[1].
1,2,4-Trimethoxybenzene (1 mM, 75-90 min) inhibits LPS and ATP-induced NLRP3 activation in iBMDMs, primary microglia, and Primary macrophages cells[1].
1,2,4-Trimethoxybenzene (75-90 min) inhibits nigericin-induced NLRP3 activation in iBMDMs and primary macrophages, while 1,2,3-TTB had no inhibitory effect, indicating that the inhibitory activity is structure-dependent[1].
1,2,4-Trimethoxybenzene (45 min-2 h) does not inhibit LPS and poly(dA:dT)-induced activation of AIM2 inflammasome in primary peritoneal macrophages and iBMDMs[1].
1,2,4-Trimethoxybenzene (1 h) reduces the formation of ASC specks in iBMDMs and Primary microglia induced by LPS and nigericin: immunofluorescence showed a significant reduction in the number of ASC specks; DSS crosslinking experiments showed an increase in soluble ASCs and a decrease in insoluble ASCs[1].
1,2,4-Trimethoxybenzene (1 h) blocks the protein-protein interaction between NLRP3 and ASC in LPS-induced iBMDMs[1].
1,2,4-Trimethoxybenzene (1 h) inhibits LPS and nigericin-induced NLRP3 oligomerization of iBMDMs and primary macrophages: DSS crosslinking experiments showed reduced formation of NLRP3 monomers, dimers and higher oligomers[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Immortalized murine bone marrow-derived macrophages (iBMDMs)
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Concentration:0.5 mM, 1 mM
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Incubation Time:1.5 h
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Result:Caspase-1 (Casp-1) cleavage and IL-1β secretion are reduced.
1,2,4-Trimethoxybenzene (50-100 mg/kg, p.o., once daily for 3 days) enhances the extinction of fear memories and alleviates PTSD-related anxiety and depression-like behaviors in mice by inhibiting the NLRP3 inflammasome[2].
1,2,4-Trimethoxybenzene (50-200 mg/kg, p.o., once daily for 8 weeks) improves T2DM-related cognitive dysfunction by inhibiting NLRP3 inflammasome activation and regulating gut microbiota in type 2 diabetic rats[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female C57BL/6 mice (6-8 weeks old) were subcutaneously injected with 150 μg of MOG35-55 peptide, and intraperitoneally injected with 200 ng of pertussis toxin on the day of immunization (day 0) and day 2, to simulate EAE[1].
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Dosage:200 mg/kg
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Administration:P.o., once daily for 17 days
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Result:The incidence of end-stage renal disease (ESRD) decreased, and clinical symptoms were significantly alleviated.
Significantly reduced weight loss indicates a reduction in systemic inflammatory response.
The area of myelin basic protein (MBP) positive in spinal cord sections was significantly larger than in the control group, indicating a reduced degree of demyelination.
The percentage of demyelinated area was significantly lower than in the control group, confirming the protection of myelin structure.
ASC specks were significantly reduced in spinal cord sections, suggesting that NLRP3 inflammasome activation was inhibited.
The expression of NLRP3, ASC, and cleaved caspase-1 proteins was downregulated in spinal cord tissue.
The mRNA expression of pro-inflammatory cytokines IFN-γ and IL-17a and the chemokine CCL-5 was decreased in the spinal cord, while the expression of the anti-inflammatory cytokine IL-4 was upregulated.
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Animal Model:Male C57BL/6 mice (8 weeks old) were intraperitoneally injected with lipopolysaccharide (LPS, 2 mg/kg/d) for 3 consecutive days to induce depressive-like behavior[2].
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Dosage:50 mg/kg, 100 mg/kg
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Administration:P.o., once daily for 3 days
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Result:Sucrose preference was significantly increased (with improved depressive-like behavior), and immobility time in the tail suspension test (TST) and forced swimming test (FST) was significantly reduced.
Activation of the hippocampal NLRP3 inflammasome was inhibited (e.g., reduced expression of cleaved IL-1β, cleaved caspase-1, and ASC spot formation).
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Animal Model:Male Sprague-Dawley rats (8 weeks old, 200 g) were first given a high-sugar, high-fat diet for 5 weeks, and then type 2 diabetes (T2DM) was induced by intraperitoneal injection of streptozotocin (STZ, 30 mg/kg)[3].
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Dosage:50 mg/kg, 100 mg/kg, 200 mg/kg
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Administration:P.o., once daily for 8 weeks
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Result:Significant improvements were observed in blood glucose levels (FBG, OGTT-AUC), insulin resistance index (HOMA-IR), and blood lipids (TC, TG, LDL-C) in rats, along with a decrease in oxidative stress markers (MDA).
Shortened escape latency and increased target quadrant time indicate enhanced learning and memory abilities.
Improved neuronal structure was observed in the hippocampal CA1 region, with ELISA detecting elevated BDNF levels and decreased AChE levels in the hippocampus.
Inhibition of the hippocampal NLRP3 inflammasome pathway (e.g., reduced expression of NLRP3, ASC, caspase-1, GSDMD, and IL-1β).
Chemical Information
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CAS No. 135-77-3
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Appearance Liquid
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Molecular Weight 168.19
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Formula C9H12O3
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SMILES
COC(C(OC)=C1)=CC=C1OC
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Store at room temperature 3 years
In solvent -80°C 2 years -20°C 1 year
Purity & Documentation
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Data Sheet (280 KB)
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SDS (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
[1]. Pan RY, et al. 1,2,4-Trimethoxybenzene selectively inhibits NLRP3 inflammasome activation and attenuates experimental autoimmune encephalomyelitis. Acta Pharmacol Sin. 2021 Nov;42(11):1769-1779. doi: 10.1038/s41401-021-00613-8IF: 8.4 Q1 . Epub 2021 Feb 24. Erratum in: Acta Pharmacol Sin. 2022 Feb;43(2):504. [Content Brief]
[2]. Zhang Y, et al. 1,2,4-Trimethoxybenzene ameliorates depression-like behaviors by inhibiting the activation of NLRP3 inflammasome. Int Immunopharmacol. 2025 Apr 4;151:114361. [Content Brief]
[3]. Zhong P, et al. 1,2,4-Trimethoxybenzene alleviates cognitive dysfunction in type 2 diabetes model rats by inhibiting NLRP3 inflammasome and restoring gut microbiota disorders. Biochem Pharmacol. 2025 Dec;242(Pt 4):117409. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)