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| Targets |
1,4‑Dihydroxy‑2‑naphthoic acid (1,4‑DHNA) inhibits glycogen synthase kinase 3beta (GSK‑3beta), a serine/threonine kinase involved in numerous cellular processes, including glycogen metabolism, cell cycle regulation, apoptosis, and neuronal function. GSK‑3beta is a key enzyme in the pathogenesis of Alzheimer‘s disease (where it phosphorylates tau protein), type 2 diabetes (where it inhibits insulin signaling), and cardiovascular diseases (where it contributes to cardiac hypertrophy and ischemic injury). 1,4‑DHNA is an orally active, non‑toxic small‑molecule inhibitor of GSK‑3beta with antioxidant properties.
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| ln Vitro |
1,4‑Dihydroxy‑2‑naphthoic acid is an orally active, non‑toxic, small‑molecule inhibitor of glycogen synthase kinase 3beta (GSK‑3beta). It has antioxidant properties and cardioprotective effects. In vitro, 1,4‑DHNA has been shown to inhibit GSK‑3beta activity, leading to the activation of downstream signaling pathways (e.g., activation of beta‑catenin). The compound has also been reported to increase glycolytic flux. No specific IC₅0 values for GSK‑3beta inhibition are reported. 1,4‑DHNA is also a key intermediate in the bacterial biosynthesis of menaquinone (vitamin K2).
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| ln Vivo |
No specific in vivo activity data for 1,4‑Dihydroxy‑2‑naphthoic acid are reported in the search results. As an orally active GSK‑3beta inhibitor with cardioprotective effects, it has potential for evaluation in animal models of Alzheimer‘s disease (e.g., transgenic tau mice), diabetes (e.g., db/db mice, STZ‑induced diabetic rats), and cardiovascular disease (e.g., ischemia‑reperfusion injury, myocardial infarction). The compound is described as non‑toxic. No specific in vivo data are provided.
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| Enzyme Assay |
The binding of 1,4‑Dihydroxy‑2‑naphthoic acid to GSK‑3beta is measured by standard in vitro kinase activity assays using purified recombinant GSK‑3beta. The compound is incubated with GSK‑3beta, ATP, and a peptide substrate (e.g., a pre‑phosphorylated GSK‑3beta substrate peptide). The reaction is allowed to proceed, and the amount of phosphorylated peptide is quantified using a fluorescence polarization (FP) or ADP‑Glo™ assay. The IC₅0 for GSK‑3beta inhibition is calculated from dose‑response curves. No specific IC₅0 values are reported. The antioxidant activity can be measured by DPPH radical scavenging assays.
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| Cell Assay |
For cellular assays, neuronal cell lines (e.g., SH‑SY5Y, PC12) or hepatocyte cell lines (e.g., HepG2) are seeded in 6‑ or 96‑well plates. Cells are treated with 1,4‑Dihydroxy‑2‑naphthoic acid at concentrations of 1‑100 uM for 6‑48 h. GSK‑3beta activity is assessed by measuring the phosphorylation of its substrates, such as beta‑catenin (p‑beta‑catenin) or tau (p‑tau), by Western blot. Antioxidant activity is assessed by measuring ROS levels using DCFH‑DA fluorescence. Cell viability is assessed by MTT or LDH assays. For cardioprotection studies, cardiomyocytes (e.g., H9c2 cells) are treated with the compound and then subjected to oxidative stress (e.g., H2O2) or hypoxia/reoxygenation, and cell viability is measured.
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| Animal Protocol |
No animal experiments for 1,4‑Dihydroxy‑2‑naphthoic acid are described in the search results. For in vivo evaluation of cardioprotection, male Sprague‑Dawley rats would be used in a model of myocardial ischemia‑reperfusion (I/R) injury. 1,4‑Dihydroxy‑2‑naphthoic acid would be administered orally at doses of 10‑100 mg/kg before ischemia. Infarct size would be measured by TTC staining. Cardiac function (e.g., ejection fraction) would be assessed by echocardiography. For neuroprotective studies, transgenic tau mice would be treated with the compound, and tau phosphorylation, neurofibrillary tangle burden, and cognitive function would be assessed. No specific data are provided.
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| ADME/Pharmacokinetics |
1,4‑Dihydroxy‑2‑naphthoic acid (C11H₈O4, MW = 204.18, purity ≥96%, CAS 31519‑22‑9) is a solid powder (white to light yellow). For storage, the powder should be kept at -20 degC for up to 3 years, sealed and protected from light. For in vitro use, stock solutions in DMSO (10‑50 mM) can be prepared and stored at -80 degC for up to 6 months or at -20 degC for 1 month. The compound is also soluble in water (1.6 mg/mL at 20degC). For in vivo oral administration, it can be formulated in 0.5% methylcellulose/0.1% Tween‑80 or in water. No detailed PK parameters are reported.
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| Toxicity/Toxicokinetics |
1,4‑Dihydroxy‑2‑naphthoic acid is described as non‑toxic. As a research‑grade compound, it is not intended for human or veterinary use. Standard laboratory safety precautions for handling chemicals should be followed. GSK‑3beta inhibitors can have both therapeutic and toxic effects depending on the context; chronic inhibition may promote tumorigenesis. No LD₅0 or formal toxicology studies are available.
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| References | |
| Additional Infomation |
1,4-Dihydroxy-2-naphthoic acid is a naphthoic acid, a product of 2-naphthoic acid with hydroxyl groups substituted at the 1 and 4 positions. It is a metabolite of Escherichia coli. It is a dihydroxy monocarboxylic acid, naphthoic acid, naphthalene glycol, and naphthoquinone compound. Functionally related to 2-naphthoic acid, it is the conjugate acid of 1,4-dihydroxy-2-naphthoic acid. 1,4-Dihydroxy-2-naphthoic acid is a metabolite found or produced in Escherichia coli (K12 strain, MG1655 strain). 1,4-Dihydroxy-2-naphthoic acid has also been reported in Propionibacterium, with relevant data available. See also: 1,4-Dihydroxy-2-naphthoic acid (note moved here).
1,4‑Dihydroxy‑2‑naphthoic acid (1,4‑DHNA) is a natural product and a key intermediate in the bacterial biosynthesis of menaquinone (vitamin K2). It is produced by many bacteria, including gut microbiota. 1,4‑DHNA has been identified as an inhibitor of glycogen synthase kinase 3beta (GSK‑3beta), a multifunctional kinase that plays a role in numerous diseases, including Alzheimer‘s disease, type 2 diabetes, depression, and cancer. The compound is also a potent antioxidant and has cardioprotective effects. 1,4‑DHNA is for research use only and has not received regulatory approval. |
| Molecular Formula |
C11H8O4
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| Molecular Weight |
204.18
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| Exact Mass |
204.042
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| CAS # |
31519-22-9
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| PubChem CID |
671
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| Appearance |
Solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
461.7±40.0 °C at 760 mmHg
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| Melting Point |
220 °C (dec.)(lit.)
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| Flash Point |
247.1±23.8 °C
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| Vapour Pressure |
0.0±1.2 mmHg at 25°C
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| Index of Refraction |
1.762
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| LogP |
2.79
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
15
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| Complexity |
253
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| Defined Atom Stereocenter Count |
0
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| SMILES |
OC(=O)C1=C(O)C2=C(C=CC=C2)C(O)=C1
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| InChi Key |
VOJUXHHACRXLTD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H8O4/c12-9-5-8(11(14)15)10(13)7-4-2-1-3-6(7)9/h1-5,12-13H,(H,14,15)
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| Chemical Name |
1,4-dihydroxynaphthalene-2-carboxylic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : 175 mg/mL (857.09 mM; with sonication)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.8976 mL | 24.4882 mL | 48.9764 mL | |
| 5 mM | 0.9795 mL | 4.8976 mL | 9.7953 mL | |
| 10 mM | 0.4898 mL | 2.4488 mL | 4.8976 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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