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| Targets |
Trehalose does not bind to a specific pharmacological receptor; rather, its cellular effects are mediated through physical interactions with biomolecules (proteins and membranes) and through modulation of cellular stress response pathways. It is an inducer of autophagy, a catabolic process that degrades damaged organelles and proteins, and has been shown to activate transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy. Trehalose also stabilizes proteins in their native conformation, preventing aggregation through preferential exclusion from the protein surface. Additionally, trehalose has been studied for its potential therapeutic effects in neurodegenerative diseases characterized by protein aggregation (e.g., Huntington's, Parkinson's, Alzheimer's) due to its ability to promote the clearance of aggregated proteins via autophagy. However, these effects are indirect and not mediated by a specific receptor. The 13C-labeled version (Trehalose-13C12) is not active in these pathways in a different manner; it is chemically identical and used as a tracer to quantify trehalose metabolism and biodistribution.
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| ln Vitro |
D-(+)-Trehalose has been extensively characterized in vitro for its biophysical and cell biological effects. It acts as a chemical chaperone, stabilizing proteins against denaturation induced by heat, freeze-thawing, or chemical stressors. In cell culture models, trehalose has been shown to induce autophagy independent of the mTOR pathway, leading to the clearance of mutant huntingtin and alpha-synuclein aggregates. For example, in HeLa cells and primary neurons, treatment with 50-100 mM trehalose for 24-48 hours results in a significant increase in LC3-II levels (a marker of autophagosomes) and a reduction in protein aggregates. Trehalose is also endocytosed by cells and can be hydrolyzed to glucose by the enzyme trehalase if present; however, many mammalian cells have low trehalase activity, allowing trehalose to accumulate intracellularly. The labeled 13C12 version is not typically used to test these effects; instead, it is used as an internal standard to quantify trehalose concentrations in biological samples via LC-MS/MS.
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| ln Vivo |
In vivo studies with unlabeled trehalose have demonstrated its potential therapeutic benefits in animal models of Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). For instance, in R6/2 mouse models of Huntington's disease, oral administration of trehalose (2% in drinking water) reduced motor deficits and extended lifespan. In a mouse model of ALS (G93A-SOD1), trehalose treatment improved motor function and reduced muscle atrophy. The protective effects are attributed to the induction of autophagy, reduction of protein aggregates, and improvement of mitochondrial function. For the 13C-labeled version (Trehalose-13C12), in vivo studies are typically pharmacokinetic or metabolic tracer studies. Animals are administered the labeled trehalose (e.g., by oral gavage or intraperitoneal injection), and blood, urine, and tissues are collected at various time points. The enrichment of 13C in trehalose and its metabolites (e.g., glucose) is measured by isotope ratio mass spectrometry (IRMS) or LC-MS/MS to determine absorption, distribution, metabolism, and excretion (ADME) parameters.
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| Enzyme Assay |
Standard protocols for receptor-binding or enzyme assays for trehalose are not common, as trehalose does not have a specific binding site on a protein receptor. However, the enzyme trehalase, which hydrolyzes trehalose into two glucose molecules, can be assayed in cell-free systems. A typical protocol: (1) Prepare a source of trehalase (e.g., purified porcine or bacterial trehalase, or a homogenate of pig kidney, which is rich in trehalase). (2) Incubate the enzyme source with D-(+)-Trehalose-13C12 (or unlabeled trehalose) as the substrate in an appropriate buffer (e.g., 50 mM sodium citrate, pH 5.5-6.0) at 37degC for varying time points (e.g., 0, 15, 30, 60, 120 minutes). (3) Stop the reaction by heating the sample at 95degC for 5 minutes or by adding perchloric acid. (4) Centrifuge to remove precipitated protein. (5) Quantify the glucose produced using a glucose assay kit (e.g., hexokinase/glucose-6-phosphate dehydrogenase method) or by HPLC. For the labeled compound, the reaction can be monitored by LC-MS/MS by tracking the decrease in the parent compound (m/z corresponding to 13C12-trehalose) and the appearance of 13C6-glucose. The kinetic parameters Km and Vmax can be derived from Lineweaver-Burk plots.
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| Cell Assay |
Cellular experiments with D-(+)-Trehalose-13C12 are not designed to assess a biological activity but rather to trace the metabolic fate of trehalose. A typical protocol for a metabolic flux study: (1) Seed mammalian cells (e.g., hepatocytes, neurons, or cancer cells) in culture plates and allow them to reach confluence. (2) Replace the culture medium with fresh medium containing a defined concentration of Trehalose-13C12 (e.g., 10-100 mM) for a specific pulse period (e.g., 1-48 hours). (3) At the end of the pulse, wash the cells twice with ice-cold PBS to remove extracellular trehalose. (4) Extract intracellular metabolites by adding ice-cold 80% methanol or 50% acetonitrile, scraping the cells, and centrifuging. (5) Dry the supernatant under a stream of nitrogen or in a speed-vacuum concentrator. (6) Reconstitute the dried extract in water or mobile phase suitable for LC-MS/MS. (7) Analyze by LC-MS/MS to detect and quantify the labeled trehalose and any labeled metabolites (such as 13C6-glucose and labeled downstream glycolytic intermediates). The relative abundance of these labeled species indicates the extent to which trehalose is taken up, hydrolyzed, and metabolized by the cells.
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| Animal Protocol |
In vivo animal experiments with D-(+)-Trehalose-13C12 are used to study the pharmacokinetics and metabolism of trehalose. A standard protocol for a mouse study: (1) Fast the animals (e.g., 8-12 week old C57BL/6 mice) for 4-6 hours prior to administration to minimize interference from dietary sugars. (2) Administer a single dose of Trehalose-13C12 to the mice by a defined route, such as oral gavage (e.g., 1-2 g/kg body weight) dissolved in sterile water or saline, or intraperitoneal injection (e.g., 200 mg/kg). (3) Collect blood samples (e.g., from the tail vein) into heparinized tubes at multiple time points: pre-dose (0), and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose. (4) Euthanize a subset of animals at each time point and harvest tissues of interest (e.g., liver, kidney, brain, muscle, small intestine). (5) Homogenize tissues in water or buffer, and deproteinize the homogenates and plasma by adding acetonitrile (3:1 v/v) followed by centrifugation. (6) Analyze the supernatants by LC-MS/MS for the concentration of the labeled trehalose and its major metabolite, 13C6-glucose. (7) Calculate pharmacokinetic parameters such as Cmax, Tmax, AUC, half-life, and bioavailability using non-compartmental analysis.
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| ADME/Pharmacokinetics |
The pharmacokinetic (PK) properties of D-(+)-Trehalose-13C12 are expected to mirror those of unlabeled trehalose, as the isotopic labeling does not alter the molecule's chemical properties. Trehalose is a hydrophilic disaccharide with a molecular weight of 354.21 for the labeled version. Following oral administration, trehalose is poorly absorbed from the gastrointestinal tract due to its polarity and susceptibility to hydrolysis by brush border trehalase in the small intestine. The absolute oral bioavailability is low (typically <1% in humans and rodents). The unabsorbed trehalose is fermented by colonic microflora. After intravenous administration, trehalose is rapidly cleared from the plasma, primarily by renal excretion and by uptake into tissues, where it is hydrolyzed to glucose by trehalase, though trehalase activity in mammalian tissues is low. The plasma half-life of trehalose in rodents following IV administration is approximately 5-15 minutes. For LC-MS/MS analysis, the labeled compound is used as an internal standard for unlabeled trehalose. Storage conditions: powder at -20degC, protected from light and under nitrogen for long-term stability (up to 3 years), and in solvent at -80degC for up to 6 months.
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| Toxicity/Toxicokinetics |
The toxicity profile of D-(+)-Trehalose-13C12 is expected to be identical to that of unlabeled trehalose, which is recognized as safe (GRAS) by the FDA and has been widely used as a food ingredient and pharmaceutical excipient for decades. Trehalose is non-toxic, non-immunogenic, and non-carcinogenic. The oral LD50 of trehalose in rats is greater than 5,000 mg/kg, indicating very low acute toxicity. At high oral doses (>1 g/kg), trehalose may cause osmotic diarrhea due to its poor absorption, similar to other non-digestible sugars. No adverse effects on reproduction, development, or genetic material have been reported. In clinical studies, intravenous trehalose has been administered safely at doses up to 1 g/kg. Importantly, individuals with trehalase deficiency (a rare genetic disorder) may experience gastrointestinal symptoms upon ingesting trehalose, as they cannot hydrolyze it efficiently, leading to malabsorption. However, for the general population, trehalose is considered extremely safe. The 13C-labeled version is intended for research use and is not intended for human consumption as a drug; however, its inherent toxicity is negligible.
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| References | |
| Additional Infomation |
D-(+)-Trehalose-13C12 (CAS 1313730-07-2) is a fully 13C-labeled isotopologue of trehalose, with 98-99 atom % 13C enrichment. The labeling is uniform across the entire carbon skeleton, resulting in a mass shift of +12 Da relative to the natural abundant molecule (342.30). This high isotopic purity makes it particularly suitable for metabolic flux analysis (MFA) and quantitative proteomics where absolute quantification of trehalose is required. In the pharmaceutical industry, trehalose is a critical excipient used to stabilize therapeutic proteins and monoclonal antibodies during lyophilization (freeze-drying), preventing aggregation and denaturation. It is also used in the preservation of cells, tissues, and organs for transplantation. The labeled version is not a drug and is not involved in any clinical trials or regulatory approvals. It is exclusively a research tool.
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| Molecular Formula |
13C12H22O11
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| Molecular Weight |
354.21
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| Exact Mass |
354.156
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| CAS # |
1313730-07-2
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| PubChem CID |
71309828
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
8
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
23
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| Complexity |
348
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| Defined Atom Stereocenter Count |
10
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| SMILES |
[13CH2]([13C@@H]1[13C@H]([13C@@H]([13C@H]([13C@H](O1)O[13C@@H]2[13C@@H]([13C@H]([13C@@H]([13C@H](O2)[13CH2]O)O)O)O)O)O)O)O
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| InChi Key |
HDTRYLNUVZCQOY-OSKVYJSUSA-N
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| InChi Code |
InChI=1S/C12H22O11/c13-1-3-5(15)7(17)9(19)11(21-3)23-12-10(20)8(18)6(16)4(2-14)22-12/h3-20H,1-2H2/t3-,4-,5-,6-,7+,8+,9-,10-,11-,12-/m1/s1/i1+1,2+1,3+1,4+1,5+1,6+1,7+1,8+1,9+1,10+1,11+1,12+1
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| Chemical Name |
(2R,3S,4S,5R,6R)-2-(hydroxy(113C)methyl)-6-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxy(113C)methyl)(2,3,4,5,6-13C5)oxan-2-yl]oxy(2,3,4,5,6-13C5)oxane-3,4,5-triol
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| Synonyms |
D-Trehalose-13C12; α,α-Trehalose-13C12
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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 | 2.8232 mL | 14.1159 mL | 28.2318 mL | |
| 5 mM | 0.5646 mL | 2.8232 mL | 5.6464 mL | |
| 10 mM | 0.2823 mL | 1.4116 mL | 2.8232 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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