phenylbutyrate   Click here for help

GtoPdb Ligand ID: 8480

Synonyms: 4-phenylbutanoic acid | Ammonaps® | Buphenyl® | gamma-phenylbutyric acid | triButyrate
Approved drug PDB Ligand
phenylbutyrate is an approved drug (FDA (1996), EMA (1999))
Compound class: Synthetic organic
Comment: The salt, sodium phenylbutyrate (PubChem CID 5258) is an inhibitor of histone deacetylase (HDAC) activity [2-3].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 2
Hydrogen bond donors 1
Rotatable bonds 4
Topological polar surface area 37.3
Molecular weight 164.08
XLogP 2.19
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES OC(=O)CCCc1ccccc1
Isomeric SMILES OC(=O)CCCc1ccccc1
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)
InChI Key OBKXEAXTFZPCHS-UHFFFAOYSA-N
No information available.
Summary of Clinical Use Click here for help
Sodium phenylbutyrate is approved to treat urea cycle disorders in patients with liver enzyme deficiency.
Phase 3 clinical trials are assessing sodium phenylbutyrate in additional metabolic disorders such as maple syrup urine disease and proteinuric diseases.
Use in rare diseases: The EMA has granted orphan drug designation for sodium phenylbutyrate as a treatment for 5q spinal muscular atrophy. The FDA includes maple syrup urine disease, spinal muscular atrophy, sickling disorders (including S-S hemoglobinopathy, S-C hemoglobinopathy, and S-thalassemia hemoglobinopathy) and primary or recurrent malignant glioma (to be used as an adjunct to chemo- and radio-therapy and surgery) as rare conditions that can be treated with sodium phenylbutyrate.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
In patients with liver enzyme deficiency hyperammonemia can develop due to impaired waste nitrogen removal. Sodium phenylbutyrate is converted to phenylacetate (active metabolite) which acts as an ammonia sink and chemical chaperone and prevents waste nitrogen from entering the urea cycle, thus preventing hyperammonemia. Sodium phenylbutyrate also acts via HDACs as a transcriptional regulator to alter chromatin structure [2]. This latter action is reported to provide neuroprotective effects [1], which may help reduce the progressive brain damage which is a major pathological symptom of metabolic disorders such as maple syrup urine disease, proteinuric diseases and other urea cycle disorders.
In 5q spinal muscular atrophy, sodium phenylbutyrate increases transcription of the SMN2 (survival of motor neuron 2) gene via inhibition of histone deacetylase activity thus effecting elevated levels of functional SMN2 protein [2].