Triheptanoin

Identification

Name
Triheptanoin
Accession Number
DB11677
Type
Small Molecule
Groups
Approved, Investigational
Description

Triheptanoin is a source of heptanoate fatty acids, which can be metabolized without the enzymes of long chain fatty acid oxidation.4 In clinical trials, patients with long chain fatty acid oxidation disorders (lc-FAODs) treated with triheptanoin are less likely to develop hypoglycemia, cardiomyopathy, rhabdomyolysis, and hepatomegaly.1,2 Complications in lc-FAOD patients are reduced from approximately 60% to approximately 10% with the addition of triheptanoin.2

Triheptanoin was granted FDA approval on 30 June 2020.4

Structure
Thumb
Synonyms
  • Glycerol triheptanoate
  • Glyceryl triheptanoate
  • Trienanthoin
  • Triheptanoic glyceride
  • Triheptanoin
  • Triheptylin
  • Trioenanthoin
External IDs
UX-007 / UX007
International/Other Brands
Dojolvi
Categories
UNII
2P6O7CFW5K
CAS number
620-67-7
Weight
Average: 428.61
Monoisotopic: 428.313789137
Chemical Formula
C24H44O6
InChI Key
PJHKBYALYHRYSK-UHFFFAOYSA-N
InChI
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
IUPAC Name
1,3-bis(heptanoyloxy)propan-2-yl heptanoate
SMILES
CCCCCCC(=O)OCC(COC(=O)CCCCCC)OC(=O)CCCCCC

Pharmacology

Indication

Triheptanoin is a medium chain triglyceride indicated to provide calories and fatty acids to treat long chain fatty acid oxidation disorders (lc-FAODs).4

Associated Conditions
Pharmacodynamics

Triheptanoin is a source of medium chain fatty acids for patients with lc-FAODs.4 It has a moderate duration of action and a wide therapeutic window.4 Patients should be counselled regarding the risk of feeding tube dysfunction and intestinal malabsorption due to pancreatic insufficiency.4

Mechanism of action

Triheptanoin is a source of heptanoate fatty acids, which can be metabolized without the enzymes of long chain fatty acid oxidation.4 In clinical trials, patients with lc-FAODs treated with triheptanoin experienced improvements in hypoglycemia, cardiomyopathy, and rhabdomyolysis.1

Absorption

A single 0.3 g/kg dose of triheptanoin reaches a Cmax of 178.9 µmol/L, with a Tmax 0.5 h, and an AUC of 336.5 µmol*h/L.4 A single 0.4 g/kg dose of triheptanoin reaches a Cmax of 259.1 µmol/L, with a Tmax 0.8 h, and an AUC of 569.1 µmol*h/L.4

Volume of distribution
Not Available
Protein binding

Triheptanoin is approximately 80% protein bound in plasma,4 likely serum albumin.3

Metabolism

Triheptanoin is hydrolysed to heptanoate, which can be further metabolized to β-hydroxypentanoate or β-hydroxybutyrate.4

Route of elimination

Triheptanoin is minimally eliminated in the urine.4

Half life

Due to multiple peak concentrations of the heptanoate metabolite, the half life of triheptanoin could not be determined.4

Clearance

A single dose of 0.3 g/kg results in a mean apparent clearance of 6.05 L/h/kg for heptanoate.4 A single dose of 0.4 g/kg results in a mean apparent clearance of 4.31 L/h/kg for heptanoate.4

Toxicity
Not Available
Affected organisms
  • Humans
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
OrlistatOrlistat can cause a decrease in the absorption of Triheptanoin resulting in a reduced serum concentration and potentially a decrease in efficacy.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Take with food. Take triheptanoin with food, liquid, or formula.

References

General References
  1. Wehbe Z, Tucci S: Therapeutic potential of triheptanoin in metabolic and neurodegenerative diseases. J Inherit Metab Dis. 2020 May;43(3):385-391. doi: 10.1002/jimd.12199. Epub 2019 Dec 12. [PubMed:31778232]
  2. Roe CR, Brunengraber H: Anaplerotic treatment of long-chain fat oxidation disorders with triheptanoin: Review of 15 years Experience. Mol Genet Metab. 2015 Dec;116(4):260-8. doi: 10.1016/j.ymgme.2015.10.005. Epub 2015 Oct 24. [PubMed:26547562]
  3. van der Vusse GJ: Albumin as fatty acid transporter. Drug Metab Pharmacokinet. 2009;24(4):300-7. doi: 10.2133/dmpk.24.300. [PubMed:19745557]
  4. FDA Approved Drug Products: Dojolvi Triheptanoin Oral Liquid [Link]
External Links
PubChem Compound
69286
PubChem Substance
347828045
ChemSpider
62497
RxNav
1313234
ChEMBL
CHEMBL4297585
ZINC
ZINC000004521897
Wikipedia
Triheptanoin
FDA label
Download (385 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Enrolling by InvitationTreatmentGLUT1DS11
0Not Yet RecruitingTreatmentMigraine1
0RecruitingTreatmentGlycogen Storage Disease Type I1
1Active Not RecruitingTreatmentEpilepsies / Glucose Metabolism Disorders / Glucose Transport Defect / Glucose Transporter Protein Type 1 Deficiency Syndrome / Glucose Transporter Type 1 Deficiency Syndrome / Glut1 Deficiency Syndrome 1, Autosomal Recessive / GLUT1DS11
1CompletedBasic ScienceGlucose Transporter Type 1 Deficiency Syndrome / Glut1 Deficiency Syndrome1
1, 2CompletedTreatmentAmyotrophic Lateral Sclerosis (ALS)1
1, 2CompletedTreatmentFrontal Lobe Hypometabolism1
1, 2WithdrawnBasic ScienceGlucose Transporter Type 1 Deficiency Syndrome / Glut1 Deficiency Syndrome1
1, 2WithdrawnTreatmentCongestive Heart Failure (CHF) / Non-ischaemic Cardiomyopathy1
2Active Not RecruitingTreatmentGlucose Transporter Type 1 Deficiency Syndrome1
2Active Not RecruitingTreatmentHuntington's Disease (HD)1
2CompletedTreatmentAdult Polyglucosan Body Disease / Glycogen Brancher Enzyme Deficiency / Glycogen Storage Disease Type IV1
2CompletedTreatmentAlternating Hemiplegia of Childhood1
2CompletedTreatmentCarnitine Palmitoyltransferase (CPT II) Deficiency / Long-chain Fatty Acid Oxidation Disorders (LC-FAOD) / Longchain 3-hydroxy-acyl-CoA Dehydrogenase (LCHAD) Deficiency / Trifunctional Protein (TFP) Deficiency / Very Long Chain Acyl-CoA Dehydrogenase (VLCAD) Deficiency1
2CompletedTreatmentCarnitine Palmitoyltransferase 2 (CPT2) Deficiency / Long-chain 3 hydroxyacylCoA Dehydrogenase (LCHAD) Deficiency / Mitochondrial Trifunctional Protein (TFP) Deficiency / Very Long-chain acylCoA Dehydrogenase (VLCAD) Deficiency1
2CompletedTreatmentGlucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)1
2CompletedTreatmentGlycogen Storage Disease Type V1
2CompletedTreatmentHuntington's Disease (HD)1
2Enrolling by InvitationTreatmentCarnitine Palmitoyltransferase (CPT I or CPT II) Deficiency / Carnitine-acylcarnitine Translocase (CACT) Deficiency / Long-chain 3-hydroxy-acyl-CoA Dehydrogenase (LCHAD) Deficiency / Trifunctional Protein (TFP) Deficiency / Very Long Chain Acyl-CoA Dehydrogenase (VLCAD) Deficiency1
2Not Yet RecruitingTreatmentGlycogen Storage Disease Type V1
2Not Yet RecruitingTreatmentRett's Syndrome1
2RecruitingTreatmentDebrancher Deficiency / GYG1 deficiency / Tarui Disease1
2RecruitingTreatmentEpilepsies / Glucose Metabolism Disorders / Glucose Transport Defect / Glucose Transporter Protein Type 1 Deficiency Syndrome / Glucose Transporter Type 1 Deficiency Syndrome / Glut1 Deficiency Syndrome 1, Autosomal Recessive / GLUT1DS11
2RecruitingTreatmentGlucose Transporter Type-1 Deficiency Syndrome (Glut1 DS)1
2RecruitingTreatmentRett's Syndrome1
2TerminatedTreatmentGlucose Transporter Type 1 Deficiency Syndrome1
3TerminatedTreatmentGlucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)1
3WithdrawnTreatmentLong-chain Fatty Acid Transport Deficiency1
Not AvailableAvailableNot AvailableACYL-CoA DEHYDROGENASE FAMILY, MEMBER 9, DEFICIENCY of / Barth Syndrome / Carnitine Palmitoyltransferase Deficiencies (CPT1, CPT2) / Glycogen Storage Disorders / Long-chain Hydroxyacyl-CoA Dehydrogenase Deficiency / Mitochondrial Trifunctional Protein Deficiency / Pyruvate Carboxylase Deficiency Disease / Very Long-chain acylCoA Dehydrogenase (VLCAD) Deficiency1
Not AvailableAvailableNot AvailableGlucose Transporter Type 1 Deficiency Syndrome (Glut1 DS) / Long-chain Fatty Acid Oxidation Disorders (LC-FAOD)1
Not AvailableNo Longer AvailableNot AvailableCitrate Transporter Deficiency / SLC13A5 Gene Mutation1
Not AvailableNo Longer AvailableNot AvailableGlucose Transporter 1 Deficiency Syndrome1
Not AvailableNo Longer AvailableNot AvailableGlucose Transporter Type 1 Deficiency Syndrome / Glut1 Deficiency Syndrome1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000415 mg/mLALOGPS
logP6.42ALOGPS
logP6.92ChemAxon
logS-6ALOGPS
pKa (Strongest Basic)-6.6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area78.9 Å2ChemAxon
Rotatable Bond Count23ChemAxon
Refractivity117.06 m3·mol-1ChemAxon
Polarizability52.67 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as triacylglycerols. These are glycerides consisting of three fatty acid chains covalently bonded to a glycerol molecule through ester linkages.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Glycerolipids
Sub Class
Triradylcglycerols
Direct Parent
Triacylglycerols
Alternative Parents
Tricarboxylic acids and derivatives / Fatty acid esters / Carboxylic acid esters / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Triacyl-sn-glycerol / Tricarboxylic acid or derivatives / Fatty acid ester / Fatty acyl / Carboxylic acid ester / Carboxylic acid derivative / Organic oxygen compound / Organic oxide / Hydrocarbon derivative / Organooxygen compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
Not Available

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. van der Vusse GJ: Albumin as fatty acid transporter. Drug Metab Pharmacokinet. 2009;24(4):300-7. doi: 10.2133/dmpk.24.300. [PubMed:19745557]

Drug created on October 20, 2016 14:39 / Updated on July 03, 2020 11:52

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