Phenylbutyric acid

Identification

Name
Phenylbutyric acid
Accession Number
DB06819
Description

A monocarboxylic acid the structure of which is that of butyric acid substituted with a phenyl group at C-4. It is a histone deacetylase inhibitor that displays anticancer activity. It inhibits cell proliferation, invasion and migration and induces apoptosis in glioma cells. It also inhibits protein isoprenylation, depletes plasma glutamine, increases production of foetal haemoglobin through transcriptional activation of the γ-globin gene and affects hPPARγ activation.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 164.2011
Monoisotopic: 164.083729628
Chemical Formula
C10H12O2
Synonyms
  • 4-Phenyl-n-butyric acid
  • 4-phenylbutyrate
  • 4-phenylbutyric acid
  • Benzenebutyric acid
  • PBA
  • Phenylbutyrate
  • γ-Phenyl-n-butyric acid
  • γ-phenylbutyric acid
  • ω-Phenylbutanoic acid
  • ω-phenylbutyric acid
External IDs
  • NSC-295

Pharmacology

Indication

Adjunctive therapy for the management of chronic urea cycle disorders due to deficiencies in carbamylphosphate (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase. it is indicated in all neonatal- onset efficiency presenting within the first 28 days of life. Also indicated in patients with late-onset, presenting after the first month of life with a history of hyperammonemic encephalopathy.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
Pharmacodynamics

Decreases elevated plasma ammonia glutamine levels

Mechanism of action

Sodium phenylbutyrate is a pro-drug that is metabolized to the active compound phenylacetate. Phenylacetate conjuages with glutamine via acetylation reaction to form the product phenylacetylglutamine, which is excreted by the kidneys. This provides an alternative mechanism for waste nitrogen excretion.

TargetActionsOrganism
UAromatic-amino-acid aminotransferaseNot AvailableParacoccus denitrificans
UThermolysinNot AvailableBacillus thermoproteolyticus
Absorption

Under fasting condition the Cmax of a single orally ingested 5g tablet and 5g powder after 1 hour are respectively 218mcg/ml and 195mcg/ml. The effect of food on phenylbutyrate absorption is still unknown.

Volume of distribution

The volume of distribution of phenylbutyrate is 0.2 l/kg.

Protein binding

phenylbutyrate and Phenylacetate concentrations in the plasma were determined by high-performance liquid chromatography. Both drugs exhibited concentration-dependent binding. Results showed sodium phenylacetate to have a higher free fraction than sodium phenylbutyrate at corresponding concentrations (> 0.442 +/- 0.008 and > 0.188 +/- 0.001, respectively). Both have high free fractions in plasma.

Metabolism

The overall disposition of sodium phenylbutyrate and its metabolites has not been characterized fully. However, the drug is known to be metabolized to phenylacetate and subsequently to phenylacetylglutamine. Metabolism of phenylbutyrate occurs mainly in liver and kidney.

Hover over products below to view reaction partners

Route of elimination

The major route of elimination is the kidneys as phenylacetylglutamine.

Half-life

For sodium phenylbutyrate the half life is 0.77 hours. For phenylacetate the half life is 1.15 hours.

Clearance

Within 24 hours 80-100% of the administered dose in eliminated in the urine as pheylacetylglutamine.

Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity

Clinical adverse reaction: In females who were menstruating, 23% reported amenorrhea or menstrual dysfunction. In all patients, 4% reported a decreased appetite, and body odor issues, and 3% of patients report a taste aversion. Other adverse events that occurred in less than 2% of patients were abdominal pain, gastritis, nausea and vomiting, constipation, rectal bleeding, peptic ulcer disease, pancreatitis, aplastic anemia, ecchymosis, arrhythmia, edema, renal tubular acidosis, depressions, skin rash, headache, syncope, and weight gain occurring in at least one patient. Laboratory adverse events: Changes to baseline laboratory values were also observed. The events include: acidosis (14%), alkalosis and hyperchloremia (7%), hypophosphatemia (6%), hyperuricemia and hyperphosphatemia (2%), hypernatremia and hypokalemia (1%), hypoalbuminemia (11%), decreased total protein (3%), increase alkaline phosphate (6%), increased liver transaminases (4%), hyperbilirubinemia (1%), anemia (9%), leukopenia and leukocytosis (4%), thrombocytopenia (3%) and thrombocytosis (1%).

Affected organisms
Not Available
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
AcebutololThe metabolism of Acebutolol can be decreased when combined with Phenylbutyric acid.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Phenylbutyric acid.
AlmotriptanThe metabolism of Almotriptan can be decreased when combined with Phenylbutyric acid.
AlogliptinThe metabolism of Alogliptin can be decreased when combined with Phenylbutyric acid.
AminophenazoneThe metabolism of Aminophenazone can be decreased when combined with Phenylbutyric acid.
AmiodaroneThe metabolism of Amiodarone can be decreased when combined with Phenylbutyric acid.
AmitriptylineThe metabolism of Amitriptyline can be decreased when combined with Phenylbutyric acid.
AmoxapineThe metabolism of Amoxapine can be decreased when combined with Phenylbutyric acid.
AmphetamineThe metabolism of Amphetamine can be decreased when combined with Phenylbutyric acid.
AmprenavirThe metabolism of Amprenavir can be decreased when combined with Phenylbutyric acid.
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.

    Learn more
  • Evidence Level
    Evidence Level

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

    Learn more
  • Action
    Action

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

    Learn more
Food Interactions
  • Take with food.

Products

Product Ingredients
IngredientUNIICASInChI Key
Sodium phenylbutyrateNT6K61736T1716-12-7VPZRWNZGLKXFOE-UHFFFAOYSA-M
Product Images
International/Other Brands
triButyrate (Fyrlklövern Scandinavia)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AmmonapsTablet500 mgOralSwedish Orphan Biovitrum Ab1999-12-08Not applicableEU flag
AmmonapsGranule940 mg/gOralSwedish Orphan Biovitrum Ab1999-12-08Not applicableEU flag
AmmonapsTablet500 mgOralSwedish Orphan Biovitrum Ab1999-12-08Not applicableEU flag
AmmonapsGranule940 mg/gOralSwedish Orphan Biovitrum Ab1999-12-08Not applicableEU flag
BuphenylPowder0.94 g/1gOralHyperion Therapeutics, Inc.1996-04-302016-11-29US flag
BuphenylTablet500 mg/1OralUcyclyd Pharma Inc.1996-05-132015-02-28US flag
BuphenylPowder0.94 g/1gOralHorizon Therapeutics USA, Inc.1996-04-30Not applicableUS flag
BuphenylTablet500 mg/1OralHyperion Therapeutics, Inc.1996-05-132016-11-29US flag
BuphenylTablet500 mg/1OralHorizon Therapeutics USA, Inc.1996-05-13Not applicableUS flag
BuphenylPowder0.94 g/1gOralUcyclyd Pharma Inc.1996-04-302015-02-28US flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Sodium PhenylbutyratePowder0.94 g/1gOralSigma Pharm Laboratories, Llc2011-11-30Not applicableUS flag
Sodium PhenylbutyrateTablet500 mg/1OralMikart, LLC2011-11-182011-11-19US flag
Sodium PhenylbutyratePowder0.94 g/1gOralPar Pharmaceutical2016-08-31Not applicableUS flag49884 00620180907 15195 1sffcv4
Sodium PhenylbutyrateTablet500 mg/1OralPar Pharmaceutical, Inc.2016-04-29Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more

Categories

ATC Codes
A16AX03 — Sodium phenylbutyrate
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as benzene and substituted derivatives. These are aromatic compounds containing one monocyclic ring system consisting of benzene.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Not Available
Direct Parent
Benzene and substituted derivatives
Alternative Parents
Monocarboxylic acids and derivatives / Carboxylic acids / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Aromatic homomonocyclic compound / Carbonyl group / Carboxylic acid / Carboxylic acid derivative / Hydrocarbon derivative / Monocarboxylic acid or derivatives / Monocyclic benzene moiety / Organic oxide / Organic oxygen compound / Organooxygen compound
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
monocarboxylic acid (CHEBI:41500)

Chemical Identifiers

UNII
7WY7YBI87E
CAS number
1821-12-1
InChI Key
OBKXEAXTFZPCHS-UHFFFAOYSA-N
InChI
InChI=1S/C10H12O2/c11-10(12)8-4-7-9-5-2-1-3-6-9/h1-3,5-6H,4,7-8H2,(H,11,12)
IUPAC Name
4-phenylbutanoic acid
SMILES
OC(=O)CCCC1=CC=CC=C1

References

General References
  1. product info [Link]
  2. FDA label [Link]
Human Metabolome Database
HMDB0000543
KEGG Drug
D05868
PubChem Compound
4775
PubChem Substance
310264895
ChemSpider
4611
RxNav
1546447
ChEBI
41500
ChEMBL
CHEMBL1469
ZINC
ZINC000000056568
PDBe Ligand
CLT
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Sodium_phenylbutyrate
PDB Entries
2ay7 / 3tz2 / 3tz5 / 5vnl / 5vnm / 5vnn / 5yoq
FDA label
Download (91.6 KB)
MSDS
Download (220 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedHealth Services ResearchDiabetes / Insulin Resistance1
4RecruitingTreatmentDeficiencies in enzymes of the urea cycle1
3CompletedTreatmentDeficiencies in enzymes of the urea cycle1
2Active Not RecruitingTreatmentAlzheimer's Disease (AD)1
2CompletedTreatmentAmino Acid Metabolism, Inborn Errors1
2CompletedTreatmentAmino Acid Metabolism, Inborn Errors / Argininosuccinic Aciduria / Deficiencies in enzymes of the urea cycle1
2CompletedTreatmentDeficiencies in enzymes of the urea cycle1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentHuntington's Disease (HD)1
2CompletedTreatmentLeukemias1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
GranuleOral940 mg/g
TabletOral500 mg
PowderOral0.94 g/1g
TabletOral500 mg/1
GranuleOral
GranuleOral483 MG/G
GranuleOral48.3 g
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)>150MSDS
water solubility100mMMSDS
Predicted Properties
PropertyValueSource
Water Solubility0.513 mg/mLALOGPS
logP2.29ALOGPS
logP2.5ChemAxon
logS-2.5ALOGPS
pKa (Strongest Acidic)4.81ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity46.57 m3·mol-1ChemAxon
Polarizability17.99 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
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
GC-MS Spectrum - EI-BGC-MSsplash10-0udl-7900000000-3308656352d708576a12
MS/MS Spectrum - Quattro_QQQ 10V, NegativeLC-MS/MSsplash10-03di-4900000000-2b18919d21183949b0f0
MS/MS Spectrum - Quattro_QQQ 25V, NegativeLC-MS/MSsplash10-0006-9000000000-6e1432dc108281f8c5fb
MS/MS Spectrum - Quattro_QQQ 40V, NegativeLC-MS/MSsplash10-0006-9100000000-9477dfafb0c27b1670ab
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
1H NMR Spectrum1D NMRNot Applicable
[1H,13C] 2D NMR Spectrum2D NMRNot Applicable

Targets

Kind
Protein
Organism
Paracoccus denitrificans
Pharmacological action
Unknown
General Function
Pyridoxal phosphate binding
Specific Function
Shows activities toward both dicarboxylic and aromatic substrates.
Gene Name
tyrB
Uniprot ID
P95468
Uniprot Name
Aromatic-amino-acid aminotransferase
Molecular Weight
42731.635 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
Kind
Protein
Organism
Bacillus thermoproteolyticus
Pharmacological action
Unknown
General Function
Metalloendopeptidase activity
Specific Function
Extracellular zinc metalloprotease.
Gene Name
npr
Uniprot ID
P00800
Uniprot Name
Thermolysin
Molecular Weight
60103.515 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da

Drug created on September 14, 2010 10:21 / Updated on June 12, 2020 10:52

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Logo pink
Stay in the know!
As part of our commitment to providing the most up-to-date drug information, we will be releasing #DrugBankUpdates with our newly added curated drug pages.
#DrugBankUpdates