3-Deoxyglucosone does not have a conventional pharmacological target but is a key reactive intermediate in non-enzymatic glycation. It rapidly reacts with the amino groups of proteins, particularly lysine and arginine residues, leading to the formation of AGEs, such as imidazolone (the most specific AGE derived from 3-DG), pyrraline, and Nε-(carboxyethyl)lysine (CEL). The AGEs generated from 3-DG bind to the receptor for advanced glycation end-products (RAGE), triggering downstream inflammatory and oxidative stress signaling pathways. Through this indirect mechanism, 3-DG contributes to cellular dysfunction, extracellular matrix stiffening, and the pathophysiology of diabetic complications including nephropathy, retinopathy, neuropathy, and cardiovascular disease. 3-DG also inactivates glutathione peroxidase, an important antioxidant enzyme, by modifying its active site, thereby reducing cellular antioxidant capacity and increasing susceptibility to oxidative damage. Additionally, 3-Deoxyglucosone has been shown to enhance glucose-dependent GLP-1 (glucagon-like peptide-1) secretion in enteroendocrine cells, suggesting a possible physiological signaling role in the gut beyond its pathological actions in glycation.

3-Deoxyglucosone (80 ng/ml-1000 ng/ml; 1 hour), the 300 ng/ml or 1000 ng/ml 3DG treatment group markedly enhanced GLP-1 secretion by 1.23-fold. However, there is no effect at lower quantities (80 ng/ml) [1]. 3. Intracellular Ca2+ levels were highly elevated by deoxyglucosone (300 ng/ml; 1 h) as measured by Fluo-3/AM (2.5 μM, 30 min). In contrast, the cAMP Elisa assay [1] shows no effect of 3DG on intracellular cAMP levels. 3. Both in glucose-free and high circumstances, deoxyglucosone (300 ng/ml; 1 hour) dramatically raises the protein expression levels of TAS1R2, TAS1R3, and TRPM5 [1].

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In vitro studies have demonstrated that 3-Deoxyglucosone rapidly reacts with proteins to form AGEs. Incubation of 3-DG with bovine serum albumin (BSA) or other model proteins results in the formation of imidazolone and other AGE structures in a time- and concentration-dependent manner, which can be monitored by fluorescence spectroscopy (excitation ~370 nm, emission ~440 nm) or by ELISA using specific anti-AGE antibodies. 3-DG has been shown to inactivate glutathione peroxidase in cell-free systems, reducing the enzyme‘s ability to detoxify hydrogen peroxide and lipid hydroperoxides. In cell culture models (e.g., endothelial cells, mesangial cells, neuronal cells), exposure to 3-DG induces cellular oxidative stress, as measured by increased production of reactive oxygen species (ROS), depletion of reduced glutathione (GSH), and activation of the transcription factor NF-kappaB (nuclear factor-kappa B), leading to the expression of pro-inflammatory cytokines (e.g., TNF-alpha, IL-6, ICAM-1). 3-DG also induces apoptosis in various cell types, as assessed by Annexin V/propidium iodide staining, activation of caspases, and DNA fragmentation assays. In enteroendocrine cell lines such as GLUTag or NCI-H716, 3-DG has been shown to synergize with low glucose to enhance GLP-1 secretion, an effect that may involve closure of ATP-sensitive potassium channels and calcium influx.

3-Deoxyglucosone (intragastric; 20 mg/kg; single dosage) enhances AUC but does not significantly alter plasma glucagon levels, hence impairing glucose tolerance. Significant islet cell dysfunction coexists with poor glucose regulation (IGR) in Kunming mice and SD rats [2]. 3-Deoxyglucosone (gastric gavage; 5–50 mg/kg; once daily; 2 weeks) basal levels in the equivalent control group compared to the colon (twice) and in the upper and lower small intestines (1.4–1.4 fold), ileum (1.4+ fold), and ileum (1.4–1.4 fold). In the duodenum and colon, there was also a notable decrease in the protein expression of TAS1R2, TAS1R3, and TRPM5 [3].

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In vivo studies in animal models of diabetes have established that 3-Deoxyglucosone levels are elevated in the plasma and tissues of hyperglycemic animals. Streptozotocin (STZ)-induced diabetic rats, as well as genetically diabetic db/db mice, exhibit significantly increased circulating and tissue 3-DG concentrations compared to normoglycemic controls. Administration of 3-DG to normoglycemic animals induces features of diabetic complications, including increased urinary albumin excretion (a marker of nephropathy) and impaired nerve conduction velocity (a marker of neuropathy), effects that are attributed to AGE formation. Conversely, treatments that lower 3-DG, such as the AGE inhibitor pyridoxamine or the dicarbonyl scavenger aminoguanidine, have been shown to reduce the accumulation of AGEs and ameliorate diabetic complications in animal models. 3-DG has also been used as a tool to induce AGE formation and protein crosslinking in vivo for mechanistic studies.

For in vitro protein glycation assays to assess AGE formation, bovine serum albumin (BSA, 10 mg/mL) is dissolved in 0.2 M phosphate buffer (pH 7.4) containing 0.02% sodium azide (to prevent microbial growth). 3-Deoxyglucosone (1-50 mM) is added to the BSA solution, and the mixture is incubated at 37degC for 1-14 days under sterile conditions. At various time points (e.g., days 1, 3, 7, 14), aliquots are removed. Glycation is monitored by: (1) Fluorescence spectroscopy - measure fluorescence at excitation 370 nm/emission 440 nm (characteristic of certain AGE structures). (2) SDS-PAGE - observe protein crosslinking (high molecular weight bands) and protein fragmentation. (3) Western blotting using specific antibodies against imidazolone, CEL, or pyrraline. (4) ELISA - use anti-AGE antibodies to quantify AGE formation. (5) LC-MS/MS - identify and quantify specific AGE structures after protein hydrolysis. To test inhibitors of glycation (e.g., aminoguanidine, pyridoxamine, metformin), these compounds are co-incubated with 3-DG and BSA, and AGE formation is compared to control incubations without inhibitor. For glutathione peroxidase (GPx) inactivation assays, purified GPx (0.5-2 U/mL) is incubated with 3-DG (0-50 mM) in 50 mM Tris-HCl buffer (pH 7.4) at 37degC for 0-60 minutes. GPx activity is measured using a coupled enzyme assay: GPx reduces H2O2 while oxidizing reduced glutathione (GSH) to oxidized glutathione (GSSG); GSSG is then reduced back to GSH by glutathione reductase (GR) with concomitant oxidation of NADPH to NADP+. The decrease in absorbance at 340 nm is monitored spectrophotometrically. Enzyme activity is expressed as units per mg protein. Control incubations without 3-DG or with known GPx inhibitor (e.g., mercaptosuccinate) are included.

Western Blot Analysis[1]
Cell Types: STC-1 Cell
Tested Concentrations: 300 ng/ml
Incubation Duration: 1 hour
Experimental Results: TAS1R2, TAS1R3 and TRPM5 expression was upregulated.

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For in vitro cellular assays to evaluate the effects of 3-Deoxyglucosone on cell function, human endothelial cells (e.g., HUVEC - human umbilical vein endothelial cells), human renal mesangial cells (HRMC), or neuroblastoma cell lines (e.g., SH-SY5Y) are cultured in appropriate media (e.g., DMEM or M199) supplemented with 10% fetal bovine serum and antibiotics. Cells are seeded in 6-well or 96-well plates (10,000-50,000 cells/well) and allowed to attach overnight. 3-Deoxyglucosone is added at concentrations ranging from 100 microM to 10 mM (physiological/pathological levels are in the low micromolar range in normoglycemia and can reach 100-500 microM in hyperglycemia; higher concentrations are used in mechanistic studies). Incubation times vary from 4 hours to 7 days depending on the endpoint. Endpoints measured include: (1) Cellular oxidative stress - DCFH-DA (2‘,7‘-dichlorofluorescin diacetate) fluorescent probe to measure ROS production; measurement of reduced glutathione (GSH) levels using a colorimetric or fluorometric assay; lipid peroxidation measured as malondialdehyde (MDA) using TBARS assay (thiobarbituric acid reactive substances). (2) AGE formation - immunocytochemistry with anti-imidazolone or anti-CEL antibodies; or cell lysis followed by Western blotting for AGE-modified proteins. (3) RAGE activation - Western blotting for downstream signaling intermediates (phospho-NF-kappaB p65, phospho-ERK1/2, phospho-p38 MAPK). (4) Inflammatory response - ELISA or qRT-PCR for TNF-alpha, IL-6, MCP-1, ICAM-1, VCAM-1. (5) Apoptosis - Annexin V-FITC/propidium iodide staining measured by flow cytometry; caspase-3/7 activity using fluorogenic substrates; TUNEL assay (terminal deoxynucleotidyl transferase dUTP nick end labeling); Western blotting for cleaved PARP and cleaved caspase-3. (6) Endothelial function - measurement of nitric oxide (NO) production using Griess reagent; permeability assays using Evans blue-labeled albumin. (7) GLP-1 secretion (for enteroendocrine cell studies) - GLUTag or NCI-H716 cells are treated with 3-DG and low glucose for 2 hours, and GLP-1 concentration in the supernatant is measured by ELISA.

Animal/Disease Models: SD rat [3]
Doses: 5, 20 and 50 mg/kg
Route of Administration: po (po (oral gavage)) one time/day; 2 weeks
Experimental Results: Can accumulate in intestinal tissue, thereby reducing GLP-1 and insulin secretion.

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For in vivo studies of 3-Deoxyglucosone-induced AGE formation and diabetic complications, two primary approaches are used. Approach 1 (Streptozotocin-induced diabetic rat model): Male Sprague-Dawley rats (200-250 g) are rendered diabetic by a single intraperitoneal injection of streptozotocin (STZ, 55-65 mg/kg in 0.1 M citrate buffer, pH 4.5). Control rats receive citrate buffer alone. Blood glucose levels are measured 72 hours post-injection; rats with glucose >250 mg/dL are considered diabetic. Diabetic rats are maintained for 4-12 weeks to allow the development of complications. Plasma and tissue (kidney, lens, nerve, aorta) levels of 3-Deoxyglucosone are measured by HPLC or LC-MS/MS. AGE levels (e.g., imidazolone, CEL) in tissues are quantified by ELISA or immunohistochemistry. Diabetic complications are assessed: (1) Nephropathy - urinary albumin excretion measured by ELISA; blood urea nitrogen (BUN) and serum creatinine as markers of renal function; kidney histology (H&E and PAS staining) to assess glomerulosclerosis and mesangial expansion. (2) Retinopathy - retinal vascular permeability using Evans blue extravasation; immunohistochemistry for AGEs and VEGF. (3) Neuropathy - motor and sensory nerve conduction velocity (MNCV, SNCV) measured using electrophysiological equipment; thermal nociception using hot plate test; intraepidermal nerve fiber density by immunostaining of skin biopsies. (4) Cardiovascular - blood pressure measured by tail-cuff plethysmography; vascular reactivity of aortic rings. Approach 2 (3-DG infusion in normoglycemic rats): Normal rats are implanted with osmotic minipumps (e.g., Alzet model 2004) that deliver 3-Deoxyglucosone (10-30 mg/kg/day) continuously for 4 weeks. Control rats receive vehicle (saline). At the end of the treatment period, the same endpoints for diabetic complications as described above are assessed. To test the efficacy of AGE inhibitors or dicarbonyl scavengers (e.g., aminoguanidine, pyridoxamine, ALT-711, metformin), these compounds are administered by oral gavage or in drinking water starting from the time of STZ injection or 3-DG infusion, and the outcomes (AGE levels, complication severity) are compared to the diabetic or 3-DG-infused control group.

3-Deoxyglucosone is an endogenous small-molecule dicarbonyl compound that is produced both intracellularly and extracellularly. Its levels in human plasma are typically 0.5-2 microM in healthy normoglycemic individuals but can increase to 5-20 microM in diabetic patients with poor glycemic control. Higher concentrations may be reached locally in tissues. In research studies, 3-DG is often used at supraphysiological concentrations (100 microM to 10 mM) to accelerate glycation and observe measurable effects within short time frames. As a reactive dicarbonyl, 3-DG has a short half-life in biological fluids due to rapid reaction with nucleophiles (protein amino groups, glutathione). The primary elimination pathway for 3-DG involves metabolism by the enzyme 3-deoxyglucosone reductase (also known as aldo-keto reductase family 1 member B1, AKR1B1) to 3-deoxyfructose. The compound can also be reduced by aldehyde reductase to 3-deoxysorbitol. Some 3-DG is excreted unchanged in the urine. The pharmacokinetics of 3-DG have been studied in the context of diabetes research, but detailed parameters such as half-life, volume of distribution, and clearance are not consistently provided in standard datasheets given its role as an endogenous metabolite rather than a drug candidate.

3-Deoxyglucosone is an endogenous reactive dicarbonyl compound that is generally well-tolerated at physiological levels. However, elevated levels of 3-DG, as seen in diabetes, are associated with increased AGE formation and are considered pathogenic contributors to diabetic complications and aging-related diseases. 3-DG and the AGEs derived from it are pro-inflammatory and cytotoxic. In vitro, exposure to millimolar concentrations of 3-DG induces apoptosis and oxidative stress in various cell types. In vivo, chronic infusion of 3-DG in normal animals induces features of diabetic complications, demonstrating its pathogenic potential. 3-DG is not a therapeutic agent, and formal toxicity studies have not been conducted for the isolated compound. The adverse effects associated with 3-DG are mediated through its downstream AGE/RAGE pathway rather than direct acute toxicity. In the context of safety assessment for medical products, 3-DG is monitored as a glucose degradation product (GDP) in peritoneal dialysis solutions and parenteral nutrition solutions, where high concentrations formed during heat sterilization have been associated with peritoneal membrane damage and other adverse effects. Regulatory limits for 3-DG content in these medical solutions exist to minimize patient exposure to reactive dicarbonyl compounds.

[1]. 3-Deoxyglucosone Induces Glucagon-Like Peptide-1 Secretion from STC-1 Cells via Upregulating Sweet Taste Receptor Expression under Basal Conditions.Int J Endocrinol. 2019 Oct 23;2019:4959646.

[2]. Acute Reduction of Incretin Effect and Glucose Intolerance in Rats by Single Intragastric Administration of 3-deoxyglucosone. Exp Clin Endocrinol Diabetes. 2017 Jan;125(1):4-11.

[3]. Accumulation of intestinal tissue 3-deoxyglucosone attenuated GLP-1 secretion and its insulinotropic effect in rats. Diabetol Metab Syndr. 2016 Nov 29;8:78.

[4]. 3-Deoxyglucosone: metabolism, analysis, biological activity, and clinical implication.J Chromatogr B Biomed Sci Appl. 1999 Aug 6;731(1):23-36.

3-Deoxyglucose ketone is a deoxyketohexose composed of the open-chain form of D-glucose, lacking the -OH group at position 3 and containing a ketone group at position 2. It is both a deoxyketohexose and a deoxyglucose.

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3-Deoxyglucosone (CAS# 4084-27-9) is a research-grade dicarbonyl compound used as an analytical reference standard and a tool in glycation, AGE, and diabetes research. It has a molecular weight of 162.14 and a molecular formula of C₆H10O₅. Synonyms include 3-deoxy-D-glucosone, 3-deoxy-D-erythro-hexos-2-ulose, and 3-DG. It is a reactive intermediate produced during the Maillard reaction and polyol pathway. 3-DG is widely used as a reference compound for the detection of glucose degradation products, glycating agents, and advanced glycation end-products in various matrices, including biological fluids (plasma, urine, tissue homogenates), pharmaceutical solutions (peritoneal dialysis fluids, parenteral nutrition), and food products. It is also employed to induce AGE formation in cell culture and animal models to study the pathophysiology of diabetic complications and to evaluate potential AGE inhibitors. 3-Deoxyglucosone is typically stored at -20degC as a solid, is soluble in water and organic solvents, and is commercially available as a reference standard with purities of 95% or higher. This compound is not an approved drug and is intended for research applications only. Its role in enhancing glucose-dependent GLP-1 secretion has also made it of interest in the study of enteroendocrine cell function and potential anti-diabetic mechanisms.

C₆H₁₀O₅

162.14

162.052

4084-27-9

114839

Typically exists as solid at room temperature

1.4±0.1 g/cm3

400.1±45.0 °C at 760 mmHg

73-75ºC

209.9±25.2 °C

0.0±2.1 mmHg at 25°C

1.512

-2.38

3

5

5

11

144

2

C1[C@@H](C(CO)OC(C1=O)O)O

ZGCHLOWZNKRZSN-NTSWFWBYSA-N

InChI=1S/C6H10O5/c7-2-4(9)1-5(10)6(11)3-8/h2,5-6,8,10-11H,1,3H2/t5-,6+/m0/s1

(4S,5R)-4,5,6-trihydroxy-2-oxohexanal

3Deoxyglucosone; 3 Deoxyglucosone

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

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

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.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*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).

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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)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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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).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)