| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
(2R)-Octyl-alpha-hydroxyglutarate targets inflammatory signaling pathways in immune cells, particularly macrophages. The parent metabolite (2R)-2-hydroxyglutarate (2-HG) is an anti-inflammatory immunometabolite that accumulates after TLR4 activation. It modulates cellular metabolism and inflammatory gene expression, promoting an anti-inflammatory phenotype. The octyl ester derivative is a cell-permeable prodrug that enters cells and is converted to the active metabolite (2R)-2-hydroxyglutarate, which then influences metabolic pathways including the tricarboxylic acid (TCA) cycle and modulates the activity of enzymes such as DNA and histone demethylases. This leads to altered gene expression profiles and suppression of pro-inflammatory mediators.
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| ln Vitro |
In vitro, (2R)-Octyl-alpha-hydroxyglutarate is a cell-permeable prodrug of (2R)-2-hydroxyglutarate (2-HG). Following cellular uptake, esterases hydrolyze the octyl ester to release free (2R)-2-HG, which then exerts anti-inflammatory effects. Studies have shown that (2R)-2-HG accumulates in macrophages after TLR4 activation and acts as an anti-inflammatory immunometabolite. (2R)-2-HG suppresses pro-inflammatory cytokine production (e.g., TNF-alpha, IL-6) and promotes the expression of anti-inflammatory markers (e.g., IL-10, Arginase-1). The octyl ester allows researchers to directly introduce (2R)-2-HG into cells to study its anti-inflammatory mechanisms.
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| ln Vivo |
In vivo, (2R)-Octyl-alpha-hydroxyglutarate sodium has been shown to possess anti-inflammatory properties. As a prodrug, the octyl ester improves cellular and tissue penetration of the polar (2R)-2-hydroxyglutarate metabolite, allowing it to reach its intracellular targets in immune cells. The compound would be expected to suppress inflammatory responses in animal models of inflammation, such as lipopolysaccharide (LPS)-induced endotoxemia, carrageenan-induced paw edema, or experimental autoimmune encephalomyelitis (EAE). However, specific in vivo studies with this exact prodrug have not been extensively published.
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| Enzyme Assay |
Cell-free assays for (2R)-2-hydroxyglutarate activity typically involve measuring its effects on dioxygenase enzymes, including TET (ten-eleven translocation) DNA demethylases and Jumonji C (JmjC) domain-containing histone demethylases. (2R)-2-HG acts as a competitive inhibitor of these enzymes by competing with the co-substrate alpha-ketoglutarate. However, (2R)-Octyl-alpha-hydroxyglutarate sodium is designed for use in cell-based assays rather than cell-free systems, as the octyl ester is a prodrug that requires cellular metabolism for activation.
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| Cell Assay |
Cell-based anti-inflammatory assay: Macrophages (e.g., RAW 264.7 murine macrophages or human THP-1-derived macrophages) are seeded in 96-well plates and pretreated with (2R)-Octyl-alpha-hydroxyglutarate sodium at various concentrations (e.g., 10-500 microM) for 1-4 hours. Cells are then stimulated with lipopolysaccharide (LPS, 10-100 ng/mL) for 6-24 hours. Pro-inflammatory cytokine levels (TNF-alpha, IL-1beta, IL-6, IL-12) are measured by ELISA in culture supernatants. Anti-inflammatory markers (IL-10, Arginase-1, CD206) are assessed by real-time PCR or Western blot. The compound should suppress pro-inflammatory cytokine production in a dose-dependent manner.
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| Animal Protocol |
In vivo inflammation model protocol: To evaluate the anti-inflammatory activity of (2R)-Octyl-alpha-hydroxyglutarate sodium, male C57BL/6 mice (6-8 weeks old) are administered the compound via intraperitoneal (i.p.) injection (e.g., 10-100 mg/kg) or oral gavage 1-2 hours before LPS challenge (e.g., 5 mg/kg, i.p.). Two hours post-LPS, blood is collected for serum cytokine analysis (TNF-alpha, IL-6, IL-1beta) by ELISA. Tissues (liver, lung) may be harvested for qPCR analysis of inflammatory gene expression. Alternatively, the compound can be tested in the carrageenan-induced paw edema model.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for (2R)-Octyl-alpha-hydroxyglutarate sodium have not been reported. As an octyl ester prodrug, the compound is designed to be cell-permeable. Following absorption, esterases in plasma and tissues are expected to cleave the octyl ester, releasing free (2R)-2-hydroxyglutarate. The liberated (2R)-2-HG is a small, polar metabolite that is likely eliminated via renal excretion. The octyl moiety is metabolized via beta-oxidation. The prodrug approach improves the cellular delivery of the otherwise poorly permeable (2R)-2-HG for research purposes.
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| Toxicity/Toxicokinetics |
Toxicity studies for (2R)-Octyl-alpha-hydroxyglutarate sodium have not been conducted. The compound is a research chemical used to study the anti-inflammatory effects of (2R)-2-hydroxyglutarate. The parent metabolite (2R)-2-HG is produced endogenously at elevated levels in certain pathological conditions (e.g., in IDH-mutant cancers), but it is also a normal immunometabolite that accumulates transiently during inflammatory responses. The compound is expected to have low toxicity at concentrations used for in vitro and in vivo research, but formal toxicological evaluation is not available.
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| References |
[1]. de Goede KE, et al. d-2-Hydroxyglutarate is an anti-inflammatory immunometabolite that accumulates in macrophages after TLR4 activation. Biochim Biophys Acta Mol Basis Dis. 2022 Sep 1;1868(9):166427.
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| Additional Infomation |
(2R)-Octyl-alpha-hydroxyglutarate sodium is not a drug and has no clinical applications or regulatory approval. It is a research-grade cell-permeable prodrug of the endogenous immunometabolite (2R)-2-hydroxyglutarate, which acts as an anti-inflammatory molecule in macrophages following TLR4 activation. The compound is used to study the role of (2R)-2-HG in immunometabolism, inflammation, and macrophage polarization. This tool enables researchers to introduce the active metabolite into cells and animals to investigate its anti-inflammatory mechanisms, including suppression of pro-inflammatory cytokine production and promotion of anti-inflammatory gene expression. Not for human use.
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| Molecular Formula |
C13H23NAO5
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| Molecular Weight |
282.31
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| Exact Mass |
282.144
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| CAS # |
1391068-16-8
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| Related CAS # |
(2R)-Octyl-α-hydroxyglutarate;1391194-67-4;(2S)-Octyl-α-hydroxyglutarate;1391194-64-1
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| PubChem CID |
71749053
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
19
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| Complexity |
245
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CCCCCCCCOC(=O)C(CCC(=O)[O-])O.[Na+]
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| InChi Key |
UZUHAPHNUWGBFM-RFVHGSKJSA-M
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| InChi Code |
InChI=1S/C13H24O5.Na/c1-2-3-4-5-6-7-10-18-13(17)11(14)8-9-12(15)16;/h11,14H,2-10H2,1H3,(H,15,16);/q;+1/p-1/t11-;/m1./s1
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| Chemical Name |
sodium;(4R)-4-hydroxy-5-octoxy-5-oxopentanoate
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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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 3.5422 mL | 17.7110 mL | 35.4221 mL | |
| 5 mM | 0.7084 mL | 3.5422 mL | 7.0844 mL | |
| 10 mM | 0.3542 mL | 1.7711 mL | 3.5422 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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