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| ln Vivo |
In five NIDDM patients with good metabolic control (HbA1C 5.0-6.2%, off metformin for 3 days) and five healthy controls, a continuous intravenous infusion of 46.6 mmol dodecanedioic acid (as 0.4 M sodium salt solution in saline) was administered over 195 min at a constant rate of 0.24 mmol/min. Plasma glucose levels significantly decreased in NIDDM patients from 7.8 ± 0.6 mM (basal) to 5.4 ± 0.8 mM at the end of the 360-min study period (P<0.05), reaching normal range, while no significant change occurred in controls (4.7 ± 0.1 to 4.4 ± 0.04 mM). [1]
Plasma insulin levels did not change significantly in either group, indicating that C12 does not stimulate insulin secretion. [1] Plasma lactate concentration significantly decreased in NIDDM patients from 3.5 ± 0.2 to 1.5 ± 0.1 mM (P<0.001), while no change was observed in controls. Blood pyruvate increased in NIDDM patients from 26.0 ± 11.6 to 99.5 ± 14.9 μM (P<0.01), with no significant change in controls. [1] Free fatty acids (FFA) decreased in diabetic patients from 1,500 ± 250 to 875 ± 341 μM (ns), while controls had basal FFA 750 ± 128 μM. [1] Plasma ketone bodies (β-hydroxybutyrate + acetoacetate) did not change significantly in either group (controls: 235 ± 6 to 241 ± 7 μmol; NIDDM: 240 ± 5 to 246 ± 6 μmol). [1] Indirect calorimetry showed no significant increase in VO₂ consumption, indicating minimal thermogenic effect. The nonprotein respiratory quotient (npRQ) decreased basally to 0.78 ± 0.02 in NIDDM, close to the theoretical RQ for C12 oxidation (0.77), suggesting C12 oxidation. [1] No significant reduction in basal plasma glucose was observed in NIDDM patients during saline infusion (control experiment). [1] |
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| Animal Protocol |
Five patients with non-insulin-dependent diabetes mellitus (NIDDM) and five healthy controls (matched for gender, age, and BMI) participated. NIDDM patients were treated with oral hypoglycemic agents (metformin 850 mg ×2 daily) which was stopped 3 days before the experiment; short-acting human insulin was administered before meals during that period. After an overnight fast, a continuous intravenous infusion of dodecanedioic acid (0.4 M sodium salt solution in saline) was administered at a constant rate of 0.24 mmol/min for 195 min using an electric syringe pump. Infusion solutions were sterilized through 0.25 μm Millipore filters before administration. Blood samples (8 mL) were taken every 15 min for 360 min. Heparinized blood was centrifuged, and plasma was frozen at -20°C. Aliquots (5 mL) were used for pyruvate analysis. Twenty-four-hour urine was collected in containers with 0.1% sodium azide. Indirect calorimetry was continuously performed starting 45 min before and for 600 min after the infusion using a Deltatrac apparatus. [1]
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| ADME/Pharmacokinetics |
The average 24-hour urinary excretion of dodecanedioic acid was 3.0 ± 0.8 mmol in NIDDM patients and 3.1 ± 0.1 mmol in controls, corresponding to approximately 6.5% and 6.7% of the administered dose (46.6 mmol), respectively. This low urinary excretion is due to tubular reabsorption. [1]
Plasma C12 concentration reached a peak after 135 min of infusion in both groups (1.2 ± 0.2 μM in both). Area under the curve (AUC) of plasma C12 was 279.9 ± 42.7 μmol in NIDDM and 219.7 ± 14.0 μmol in controls (P = ns). [1] Urinary urea loss over 24 h was 4.8 ± 1.0 g in NIDDM and 5.1 ± 1.1 g in controls (within normal range, ns). [1] |
| Toxicity/Toxicokinetics |
Interactions
At a concentration of 1.0 mmol, dicarboxylic acids reduced the neuromuscular inhibitory effect of 10⁻⁶ mmol D-tuboCularine in isolated rat hemidiaphragmatic nerve. The β-oxidation rate of dodecanoic acid in rat liver homogenate was determined by simultaneously measuring the change in the rate of incubation of C6-C12 dicarboxylic acids with dodecanoic acid over time. In clofibrate-treated rat liver homogenate, the β-oxidation rate of C8-C12 dicarboxylic acids was significantly increased. 2.0 mmol cyanide did not inhibit the β-oxidation rate but slightly increased it in homogenates from normal rats and clofibrate-treated rats. These results strongly suggest the presence of β-oxidation of dicarboxylic acids in the peroxisome. No significant adverse effects or toxicity were reported. Urinary nitrogen loss was within normal range. The infusion was well tolerated. No mention of LD50, hepatotoxicity, nephrotoxicity, or other toxicity parameters. [1] |
| References | |
| Additional Infomation |
Dodecanoic acid is an α,ω-dicarboxylic acid, a product of the oxidation of the methyl group in dodecane to the corresponding carboxylic acid. It is an EC 1.1.1.1 (alcohol dehydrogenase) inhibitor and a human metabolite. It is an α,ω-dicarboxylic acid and dicarboxylic acid fatty acid, the conjugate acid of dodecanoic acid ester (2-), derived from the hydride of dodecane. Dodecanoic acid has been reported in fruit flies, humans, and several other organisms with relevant data. See also: Nylon 612 (molecular weight 14000) (monomer); Nylon 612 (molecular weight 18000) (monomer).
Dodecanedioic acid (C12) is a dicarboxylic acid that serves as an alternate fuel substrate. Its β-oxidation yields acetyl-CoA and succinyl-CoA, the latter entering the Krebs cycle and potentially supporting gluconeogenesis. In NIDDM patients, C12 infusion decreased plasma glucose to normal range without affecting insulin levels, reduced lactate, and increased pyruvate, suggesting increased gluconeogenesis from pyruvate and glycogen formation. C12 has very low urinary excretion (≈6.5-6.7%) compared to other dicarboxylic acids like sebacate (up to 45%), making it more suitable for clinical use. It is water-soluble, can be administered intravenously, and has minimal thermogenic effect. Potential clinical applications include parenteral nutrition and treatment of NIDDM where glucose oxidation is impaired. [1] |
| Molecular Formula |
C12H22O4
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|---|---|
| Molecular Weight |
230.3
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| Exact Mass |
230.151
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| CAS # |
693-23-2
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| Related CAS # |
Dodecanedioic acid-d20;89613-32-1;Dodecanedioic acid-d4;97543-02-7
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| PubChem CID |
12736
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| Appearance |
White to off-white solid powder
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
394.0±0.0 °C at 760 mmHg
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| Melting Point |
127-129 °C(lit.)
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| Flash Point |
216.6±17.7 °C
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| Vapour Pressure |
0.0±1.9 mmHg at 25°C
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| Index of Refraction |
1.475
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| LogP |
2.92
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
16
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| Complexity |
179
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
TVIDDXQYHWJXFK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C12H22O4/c13-11(14)9-7-5-3-1-2-4-6-8-10-12(15)16/h1-10H2,(H,13,14)(H,15,16)
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| Chemical Name |
dodecanedioic acid
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| Synonyms |
1,10-Decanedicarboxylic acid 1,12-Dodecanedioic acid 1,10-Dicarboxydecane
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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) |
DMSO : ~100 mg/mL (~434.22 mM)
H2O : < 0.1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (10.86 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (10.86 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (10.86 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.3422 mL | 21.7108 mL | 43.4216 mL | |
| 5 mM | 0.8684 mL | 4.3422 mL | 8.6843 mL | |
| 10 mM | 0.4342 mL | 2.1711 mL | 4.3422 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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