| Size | Price | Stock | Qty |
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| 100mg |
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| 500mg |
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| 1g |
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| 2g |
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Triheptanoin ( IND-106011; UX-007; Dojolvi) is a novel and potent fatty acid metabolic modulator and a triglyceride used for the treatment of inherited metabolic diseases, epilepsy, ventricular hypertrophy and myocardial glucose oxidation. As of 2020, it has been approved by FDA for the treatment of children and adults with molecularly confirmed long-chain fatty acid oxidation.disorders.
| ln Vivo |
Triheptanoin is an anaplerotic chemical that can be used to bypass enzymatic flaws that obstruct long-chain amplification oxidation (LC-FAOD) by providing latent and amplifying enzymes [1]. When using calcium supplements synergistically, triheptanoin may be utilized to treat telangiectasia. By adding extra coenzyme A and propionyl coenzyme A to their TCA, along with the trianatomy (TCA) cycle intermediate enanthate (C7), triheptanoin functions as an anaplerotic agent. Triheptanoate supports the energetic hypothesis of Alzheimer's disease by increasing brain ATP consumption and mitochondrial dysfunction, including respiration and redox balance in models of the disease [2]. In the hippocampus formation of pilot pilocarpine-induced galvanic states, rats treated with triheptanoic acid (35E%) for 10 days before to pilocarpine administration maintained mitochondrial function [3].
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| Animal Protocol |
Animal/Disease Models: 7-8 week old male CD1 (35-40 g)[3]
Doses: 35E% oral triheptanoic acid mixed into mouse feed Route of Administration: 35E% triheptanoic acid treatment was given 10 days before SE induction Experimental Results: Mitochondrial function was preserved in SE mice. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Following a single dose of 0.3 g/kg triheptanyl glycerol, the peak plasma concentration (Cmax) was 178.9 µmol/L, the time to peak concentration (Tmax) was 0.5 h, and the area under the curve (AUC) was 336.5 µmolh/L. Following a single dose of 0.4 g/kg triheptanyl glycerol, the peak plasma concentration (Cmax) was 259.1 µmol/L, the time to peak concentration (Tmax) was 0.8 h, and the AUC was 569.1 µmolh/L. Triheptanyl glycerol is excreted in very small amounts in the urine. Following a single dose of 0.3 g/kg, the mean apparent clearance of heptanyl glycerol was 6.05 L/h/kg. Following a single dose of 0.4 g/kg, the mean apparent clearance of heptanyl was 4.31 L/h/kg. Metabolism/Metabolites Triheptanoic acid glyceride hydrolyzes to heptanoic acid, which can be further metabolized to β-hydroxyvalerate or β-hydroxybutyrate. Biological Half-Life Because heptanoic acid metabolites have multiple peak concentrations, the half-life of triheptanoic acid glyceride cannot be determined. |
| Toxicity/Toxicokinetics |
Hepatotoxicity
Elevated serum enzyme levels are common during trihexanol treatment, primarily reflecting the accumulation of toxic fatty acid products in muscles and the liver, as well as potential energy deficiency. In pre-registration studies, 81% of treated subjects experienced elevated creatine phosphokinase (CPK), 72% experienced elevated alanine aminotransferase (ALT), and 68% experienced elevated aspartate aminotransferase (AST). Of these, 47% of subjects had CPK levels exceeding 5 times the upper limit of normal (ULN), 24% had ALT levels exceeding 5 times the ULN, and 15% had AST levels exceeding 5 times the ULN. However, these changes were not caused by trihexanol or medium-chain triglyceride (MCT) treatment, but rather by underlying metabolic disorders and mitochondrial dysfunction. In small trials of trihexanol for other inherited metabolic disorders, no changes in laboratory parameters were reported during supplemental treatment. Despite limited clinical experience with trihexanol since its approval and widespread use, no clinically significant cases of liver injury have been published in association with this drug. Probability Score: E (Unlikely to be the cause of clinically obvious liver damage). Protein Binding Triheptanoic acid glyceride has a protein binding rate of approximately 80% in plasma, primarily binding to serum albumin. |
| References |
[1]. Matt Shirley. Triheptanoin: First Approval. Drugs. 2020 Oct;80(15):1595-1600.
[2]. A J Yeo, et al. An anaplerotic approach to correct the mitochondrial dysfunction in ataxia-telangiectasia (A-T). Mol Metab. 2021 Dec;54:101354. [3]. Kah Ni Tan, et al. Triheptanoin protects against status epilepticus-induced hippocampal mitochondrial dysfunctions, oxidative stress and neuronal degeneration. J Neurochem. 2018 Feb;144(4):431-442. |
| Additional Infomation |
Triheptanoic acid glyceride is a source of heptanoic acid fatty acids, which can be metabolized without the involvement of long-chain fatty acid oxidases. Clinical trials have shown that patients with long-chain fatty acid oxidation disorders (lc-FAODs) treated with triheptanoic acid glyceride have a lower risk of hypoglycemia, cardiomyopathy, rhabdomyolysis, and hepatomegaly. The incidence of complications in lc-FAOD patients decreased from approximately 60% to approximately 10% after the addition of triheptanoic acid glyceride. Triheptanoic acid glyceride was approved by the FDA on June 30, 2020. Triheptanoic acid glyceride is a medium-chain triglyceride. Triheptanoic acid glyceride is a synthetic medium-chain triglyceride specifically developed for nutritional support in patients with long-chain fatty acid oxidation disorders. Triheptanoic acid glyceride is administered orally via feeding tube, with the dosage adjusted according to 30% of the daily caloric requirement. Treatment with triheptanoic acid glyceride is not associated with elevated serum transaminase or bilirubin levels or clinically significant liver injury. Drug Indications Triheptanylglycerol is a medium-chain triglyceride used to provide energy and fatty acids for the treatment of long-chain fatty acid oxidation disorders (lc-FAODs). FDA Label Mechanism of Action Triheptanylglycerol is a source of heptanyl fatty acids, which are metabolized without the involvement of long-chain fatty acid oxidases. In clinical trials, patients with lc-FAODs treated with triheptanylglycerol experienced improvements in hypoglycemia, cardiomyopathy, and rhabdomyolysis. Pharmacodynamics Triheptanylglycerol is a source of medium-chain fatty acids for patients with lc-FAODs. It has a moderate duration of action and a wide therapeutic window. Patients should be informed of the risk of feeding tube dysfunction and malabsorption due to pancreatic insufficiency.
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| Molecular Formula |
C24H44O6
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|---|---|
| Molecular Weight |
428.61
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| Exact Mass |
428.313
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| CAS # |
620-67-7
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| PubChem CID |
69286
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| Appearance |
Colorless to light yellow liquid（Density：0.904 g/cm3）
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| Density |
1.0±0.1 g/cm3
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| Boiling Point |
470.0±12.0 °C at 760 mmHg
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| Flash Point |
195.5±19.6 °C
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| Vapour Pressure |
0.0±1.2 mmHg at 25°C
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| Index of Refraction |
1.457
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| LogP |
7.73
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
23
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| Heavy Atom Count |
30
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| Complexity |
421
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCCCCCC(=O)OCC(COC(=O)CCCCCC)OC(=O)CCCCCC
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| InChi Key |
PJHKBYALYHRYSK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H44O6/c1-4-7-10-13-16-22(25)28-19-21(30-24(27)18-15-12-9-6-3)20-29-23(26)17-14-11-8-5-2/h21H,4-20H2,1-3H3
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| Chemical Name |
2,3-di(heptanoyloxy)propyl heptanoate
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| Synonyms |
TriheptanoinIND106011 UX-007 IND-106011IND 106011 UX007 UX 007 Glycerol trienanthate
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~50 mg/mL (~116.66 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.83 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 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 (5.83 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 (5.83 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 | 2.3331 mL | 11.6656 mL | 23.3312 mL | |
| 5 mM | 0.4666 mL | 2.3331 mL | 4.6662 mL | |
| 10 mM | 0.2333 mL | 1.1666 mL | 2.3331 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.
Diet Treatment Glucose Transporter Type 1 Deficiency (G1D)
CTID: NCT03181399
Phase: Phase 2 Status: Active, not recruiting
Date: 2024-01-26
Products are for research use only; We do not sell to patients
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