Homogentisic acid
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Homogentisic acid is an orally active, blood-brain barrier-permeable amyloidogenic compound that functions as both an amyloid component and a pigment precursor. Accumulation of homogentisic acid downregulates tight junction proteins (such as claudin-5, occludin, ZO-1) and impairs blood-brain barrier integrity. Homogentisic acid and its oxidation product benzoquinone acetic acid not only induce the aggregation and fibrosis of multiple proteins (such as Aβ1-42, α-synuclein, SAA, Transthyretin (TTR), atrial natriuretic peptide), but also trigger oxidative stress, damage to the Wnt/β-catenin pathway, and neurotoxicity, leading to ochronosis pigment deposition and synaptic dysfunction. At specific concentrations, homogentisic acid exerts no cytotoxicity or genotoxicity on human peripheral blood lymphocytes, and even counteracts the genotoxicity induced by Irinotecan (HY-16562). Homogentisic acid serves as an important tool molecule for investigating the mechanisms of diseases including ochronosis, secondary amyloidosis, Alzheimer's disease, and colorectal cancer.
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- Pureza: 99.68%
- No. CAS: 451-13-8
- Fòrmula: C8H8O4
- Peso molecular:168.15
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Almacenamiento:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Chemical Information
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Solvente y solubilidad
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Actividad biológica
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NPR-A |
Homogentisic acid (0.165-0.33 mM; 37 °C; 2-6 d) induces time- and dose-dependent aggregation of Aβ1-42 peptide, α-Syn, and Ttr proteins. During days 2-6, homogentisic acid reduces the monomer level of Aβ1-42 and increases high molecular weight (HMW) aggregates; after days 7-14, homogentisic acid generates a unique 24 kDa product from α-Syn; and during days 1-5, homogentisic acid elevates oligomer levels[1].
Homogentisic acid (0.33 mM; 37 °C; 14 d+14 d) increases the abundance and maturity of SAA amyloid fibrils, forming thick filament bundles and slender protofibrils, and promotes further growth of pre-aggregated SAA fibrils upon re-stimulation; it also induces α-Syn protein to form protofibrillar aggregates, spherical oligomers, and curvilinear fibrils[1].
Homogentisic acid (0.165-0.66 mM; 37 °C; 7 d for α-Syn assay, 14 d for SAA assay) promotes the formation of benzoquinone acetic acid (BQA)-protein adducts in α-Syn after 7 days and in SAA after 14 days[1].
Homogentisic acid (0.01 μM) induces Aβ aggregation in HT22 neuronal cells, SY5Y neuronal cells, and primary neuron cultures without significant cytotoxicity[2].
Homogentisic acid (0.01-0.5 μM) downregulates tight junction proteins (claudin-5, occludin, ZO-1) in a dose-dependent manner, disrupts junctional structures, and directly impairs the integrity of the blood-brain barrier in primary brain microvascular endothelial cells (BMECs)[2].
Homogentisic acid (0.01 μM; 18 h) transcriptionally suppresses the expression of tight junction proteins (claudin-5, occludin, ZO-1) in HT22 and SY5Y neuronal cells[2].
Homogentisic acid (400 μM; pH 7.45) catalyzes the co-oxidation of ascorbic acid, producing H2O2 and synergistically increasing oxygen consumption[6].
Homogentisic acid (500 μM; 30-90 min) and Fe3+-EDTA generate hydroxyl radicals, and SOD promotes the production of such radicals, whereas catalase, thiourea and sodium formate inhibit their production. Fe3+-EDTA also depolymerizes hyaluronic acid, and hydroxyl radical scavengers and catalase inhibit this degradation process[6].
Homogentisic acid (0.046 mM; 3 w) induces intracellular ochronotic pigment deposition in primary human articular osteoblasts[8].
Homogentisic acid (0.046 mM; 2-4 w) reduces the level of free thiols in primary human articular osteoblasts, decreasing this level by 20% after 2 weeks of treatment and by 50% after 3 and 4 weeks of treatment[8].
Homogentisic acid (0.046 mM; 2-4 w) impairs the Wnt/β-catenin pathway in primary human articular osteoblasts; it increases β-catenin levels by 80% after 2 weeks, while it reduces β-catenin levels by 60% and 40% after 3 and 4 weeks, respectively, and simultaneously increases its phosphorylation levels by 100% and 50%, respectively[8].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HT22 neuronal cells, SY5Y neuronal cells
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Concentration:0.01 μM
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Incubation Time:18 h
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Result:Significantly reduced claudin-5, occludin, and ZO-1 mRNA levels in both HT22 and SY5Y cells.
Homogentisic acid (16 mg/kg; tail vein injection; single dose) can efficiently cross the blood-brain barrier of healthy C57BL/6 mice[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:APP/PS1 transgenic mice, P301S transgenic mice (2-3 months old, 20-25 g, Alzheimer's disease modeling)[2]
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Dosage:20 mg/kg; 50 mg/kg
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Administration:oral gavage; five consecutive days per week; 6 weeks
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Result:Significantly decreased the novel object recognition discrimination index (50 mg/kg).\nReduced Morris water maze platform crossings and time spent in the target quadrant (20 mg/kg, 50 mg/kg).\n
Significantly shortened auditory fear conditioning freezing time (20 mg/kg, 50 mg/kg).
Downregulated cortical levels of tight junction proteins claudin-5, occludin, and ZO-1, with the greatest reduction observed at 50 mg/kg (20 mg/kg, 50 mg/kg).\n
Caused discontinuous ZO-1 staining and increased blood-brain barrier permeability (measured via Evans Blue extravasation) (50 mg/kg).
Significantly increased cerebral Aβ burden compared with controls (50 mg/kg).\n
Reduced cortical levels of synaptic proteins PSD93 and synaptophysin, with the greatest reduction observed at 50 mg/kg.
Exacerbated cognitive deficits in P301S mice, but effects were less pronounced than in APP/PS1 mice.
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Animal Model:C57BL/6 mice (2-3 months old, 20-25 g, male)[2]
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Dosage:16 mg/kg
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Administration:tail vein injection; single dose
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Result:Achieved significantly greater concentrations in brain tissue than in vehicle controls, demonstrating efficient blood-brain barrier penetration.
Chemical Information
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No. CAS 451-13-8
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Appearance Solid
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Peso molecular 168.15
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Fòrmula C8H8O4
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Color White to yellow
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SMILES
O=C(O)CC1=CC(O)=CC=C1O
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Structure Classification
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Initial Source
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvente y solubilidad
DMSO : 100 mg/mL (594.71 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
H2O : 100 mg/mL (594.71 mM; Need ultrasonic)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (14.87 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (14.87 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Working solution concentration: 0.22 mg/mL
This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.
Pureza y Documentación
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Ficha de datos (284 KB)
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SDS (396 KB)
- English - EN (396 KB)
- Français - FR (396 KB)
- Deutsch - DE (396 KB)
- Norwegian - NO (396 KB)
- Español - ES (396 KB)
- Swedish - SV (396 KB)
- Italian - IT (396 KB)
- Portuguese - PT (396 KB)
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Instrucciones de manejo (2659 KB)
Referencias
[1]. Braconi D, et al. Homogentisic acid induces aggregation and fibrillation of amyloidogenic proteins. Biochim Biophys Acta Gen Subj. 2017;1861(2):135-146. [Content Brief]
[2]. Liu X, et al. Homogentisic Acid Disrupts the Blood-Brain Barrier and Promotes Aβ Aggregation in Alzheimer's Disease. Curr Med Sci. Published online February 5, 2026. [Content Brief]
[3]. Zannoni VG, et al. Oxidation of homogentisic acid to ochronotic pigment in connective tissue. Biochim Biophys Acta. 1969 Feb 18;177(1):94-105. [Content Brief]
[4]. MILCH RA, et al. Atmospheric oxidation of homogentisic acid: spectrophotometric studies. Science. 1957 Aug 2;126(3266):209-10. [Content Brief]
[5]. Huong DT, et al. Homogentisic acid derivatives from Miliusa balansae. J Nat Prod. 2004;67(3):445-447. [Content Brief]
[6]. Martin JP Jr, et al. Homogentisic acid autoxidation and oxygen radical generation: implications for the etiology of alkaptonuric arthritis. Free Radic Biol Med. 1987;3(4):241-250. [Content Brief]
[7]. Bory C, et al. Diagnosis of alcaptonuria: rapid analysis of homogentisic acid by HPLC. Clin Chim Acta. 1990;189(1):7-11. [Content Brief]
[8]. Schiavone ML, et al. Homogentisic acid affects human osteoblastic functionality by oxidative stress and alteration of the Wnt/β-catenin signaling pathway. J Cell Physiol. 2020;235(10):6808-6816. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO / H2O | 1 mM | 5.9471 mL | 29.7354 mL | 59.4707 mL | 148.6768 mL |
| 5 mM | 1.1894 mL | 5.9471 mL | 11.8941 mL | 29.7354 mL | |
| 10 mM | 0.5947 mL | 2.9735 mL | 5.9471 mL | 14.8677 mL | |
| 15 mM | 0.3965 mL | 1.9824 mL | 3.9647 mL | 9.9118 mL | |
| 20 mM | 0.2974 mL | 1.4868 mL | 2.9735 mL | 7.4338 mL | |
| 25 mM | 0.2379 mL | 1.1894 mL | 2.3788 mL | 5.9471 mL | |
| 30 mM | 0.1982 mL | 0.9912 mL | 1.9824 mL | 4.9559 mL | |
| 40 mM | 0.1487 mL | 0.7434 mL | 1.4868 mL | 3.7169 mL | |
| 50 mM | 0.1189 mL | 0.5947 mL | 1.1894 mL | 2.9735 mL | |
| 60 mM | 0.0991 mL | 0.4956 mL | 0.9912 mL | 2.4779 mL | |
| 80 mM | 0.0743 mL | 0.3717 mL | 0.7434 mL | 1.8585 mL | |
| 100 mM | 0.0595 mL | 0.2974 mL | 0.5947 mL | 1.4868 mL |
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
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