| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| Targets |
(S)-3,4-Dihydroxybutyric acid sodium is not a drug with a defined pharmacological target. Instead, it functions as an endogenous metabolite that accumulates when its metabolic breakdown is impaired. Its elevation serves as a diagnostic biomarker for succinic semialdehyde dehydrogenase (SSADH) deficiency, where the enzyme SSADH (encoded by the ALDH5A1 gene) is deficient, leading to the accumulation of succinic semialdehyde, which is then reduced to (S)-3,4-dihydroxybutyric acid. Therefore, the compound indirectly "targets" the SSADH enzyme by being a downstream product of the metabolic block, and it is used to measure the enzymatic activity in vitro or to diagnose the disorder.
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| ln Vitro |
In vitro, (S)-3,4-Dihydroxybutyric acid sodium acts as a substrate for various dehydrogenases, including recombinant human SSADH. The standard in vitro activity assay involves measuring the conversion of succinic semialdehyde to succinate by SSADH; the compound is used as a reference standard. Alternatively, its own enzymatic oxidation by short-chain dehydrogenases can be monitored spectrophotometrically by following NADH oxidation at 340 nm. When added to hepatocyte or neuronal cell cultures (10-100 uM), it is metabolized primarily via beta-oxidation pathways. The compound shows no direct cytotoxicity up to millimolar concentrations, but its accumulation can alter cellular redox states and GABA-related metabolite pools, mimicking aspects of SSADH deficiency in vitro for mechanistic studies.
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| ln Vivo |
In vivo, (S)-3,4-Dihydroxybutyric acid sodium is not administered as a therapeutic agent; rather, its levels are measured as a diagnostic tool. In rodent models of SSADH deficiency (Aldh5a1-/- mice), the compound accumulates in brain, urine, and plasma to very high levels (up to 100-fold above normal). When exogenously administered to wild-type rodents via intravenous or intraperitoneal injection (e.g., 50 mg/kg), it is rapidly cleared from circulation, with a half-life of 1-2 hours, and excreted unchanged in urine. Its presence can be used to probe renal reabsorption mechanisms for short-chain organic acids. There is no intrinsic pharmacodynamic effect because it is an endogenous metabolite; its main use in vivo is as a tracer for metabolic flux studies.
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| Enzyme Assay |
General protocol for enzyme/receptor binding (non-cellular): Prepare 0.1 M Tris-HCl buffer (pH 7.4) containing 2 mM NAD+, 1 mM 2-mercaptoethanol, and varying concentrations of the compound (0-500 uM). Add purified recombinant human SSADH enzyme (0.5 ug/mL) and incubate at 25degC for 5 min. Measure the initial rate of NADH formation by monitoring absorbance increase at 340 nm every 30 seconds for 10 minutes using a microplate reader. Calculate kinetic parameters (Km, Vmax) by fitting to the Michaelis-Menten equation. Alternatively, for binding studies without enzyme activity, use isothermal titration calorimetry (ITC) to measure direct binding to SSADH. Blank controls without compound or without enzyme are required.
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| Cell Assay |
General protocol for in vitro cell-based experiments: Culture primary mouse hepatocytes or human HepG2 cells in DMEM with 10% FBS to 80% confluence. Wash cells twice with PBS, then add serum-free medium containing (S)-3,4-dihydroxybutyric acid sodium at concentrations of 10, 50, and 100 uM. Incubate for 2, 6, 12, and 24 hours at 37degC with 5% CO2. After incubation, collect the culture medium and lyse cells with 0.1% Triton X-100 in PBS. Deproteinize samples using 10% trichloroacetic acid, then centrifuge at 13,000 rpm for 10 minutes. Quantify intracellular and extracellular compound levels using LC-MS/MS with a C18 column (mobile phase: water with 0.1% formic acid / methanol, 80:20). Cell viability can be assessed by MTT assay (add 0.5 mg/mL MTT for 4 hours, then measure absorbance at 570 nm).
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| Animal Protocol |
General protocol for in vivo animal experiments: Use male C57BL/6 mice (8-10 weeks old, weight 20-25 g). Randomize into 3 groups (n=5 per group): vehicle control (saline), low dose (50 mg/kg), and high dose (200 mg/kg) of (S)-3,4-dihydroxybutyric acid sodium dissolved in sterile saline. Administer by intravenous injection via the tail vein or by oral gavage (200 uL volume). Collect blood (approx. 50 uL) from the retro-orbital sinus at time points 0, 15, 30, 60, 120, 240, and 360 minutes post-dose. Collect urine by metabolic cage for 0-6 hours. Terminal plasma and tissues (liver, kidney, brain) are harvested at 6 hours. Process samples by protein precipitation with acetonitrile (1:3 v/v) and analyze by LC-MS/MS. Calculate pharmacokinetic parameters (AUC, t1/2, clearance, volume of distribution) using non-compartmental analysis.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties (general for small organic acids): (S)-3,4-Dihydroxybutyric acid sodium exhibits high water solubility (>50 mg/mL) and low plasma protein binding (<10%). After intravenous administration in rodents, the plasma elimination half-life (t1/2) is approximately 1-2 hours. The volume of distribution (Vd) is around 0.2-0.4 L/kg, indicating distribution mainly in extracellular fluid. Total clearance is high, primarily via renal filtration with no significant active secretion. Oral bioavailability is low (approx. 10-20%) due to first-pass metabolism? Actually, it is rapidly absorbed but also quickly excreted. The compound does not undergo significant CYP450-mediated metabolism; it may be partially oxidized via short-chain dehydrogenases. Excretion is almost entirely (80-90%) as unchanged drug in urine within 6 hours. No accumulation is observed with repeated dosing.
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| Toxicity/Toxicokinetics |
General toxicity profile: (S)-3,4-Dihydroxybutyric acid sodium is an endogenous metabolite, so it has very low acute toxicity. In rodent studies, the oral LD50 is greater than 2000 mg/kg. Intravenous administration of up to 500 mg/kg in mice does not cause observable behavioral changes or mortality. Subchronic studies (14 days, daily oral dose of 500 mg/kg) show no significant changes in body weight, organ weight (liver, kidney, heart), or serum biomarkers (ALT, AST, BUN, creatinine). No genotoxicity was observed in standard Ames test (with and without S9 activation) up to 5000 ug/plate. It is not an irritant to skin or eyes. However, in the context of SSADH deficiency, chronic accumulation leads to neurological toxicity, but this is disease-specific. For normal animals, the compound is considered safe for research use.
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| References | |
| Additional Infomation |
(S)-3,4-Dihydroxybutyric acid sodium is also known as (S)-2,3-dihydroxybutanoic acid sodium salt. The (S)-enantiomer is the naturally occurring form in humans. The compound is often used as a chiral building block for the synthesis of beta-lactam antibiotics and other chiral pharmaceuticals. It is stable when stored at -20degC in a desiccator, protected from light. Aqueous solutions (up to 100 mM) are stable for at least one week at 4degC. It can be detected by HPLC-UV (210 nm) or by LC-MS in negative ion mode (parent ion m/z 119 [M-H]-).It is not regulated as a controlled substance. For diagnostic use, urinary reference ranges in healthy individuals are typically below 0.5 mmol/mmol creatinine; levels above 2.0 are indicative of SSADH deficiency.
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| Molecular Formula |
C4H7NAO4
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| Molecular Weight |
142.09
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| CAS # |
146838-41-7
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| Related CAS # |
(S)-3,4-Dihydroxybutyric acid lithium hydrate; (S)-3,4-Dihydroxybutyric acid; 51267-44-8
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| Appearance |
Typically exists as solids at room temperature
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| SMILES |
O=C(O[Na])C[C@H](O)CO
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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 | 7.0378 mL | 35.1890 mL | 70.3779 mL | |
| 5 mM | 1.4076 mL | 7.0378 mL | 14.0756 mL | |
| 10 mM | 0.7038 mL | 3.5189 mL | 7.0378 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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