Ligand id: 8480

Name: phenylbutyrate

Structure and Physico-chemical Properties

2D Structure
Calculated Physico-chemical Properties
Hydrogen bond acceptors 2
Hydrogen bond donors 1
Rotatable bonds 4
Topological polar surface area 37.3
Molecular weight 164.08
XLogP 4.22
No. Lipinski's rules broken 0

Molecular properties generated using the CDK

No information available.
Summary of Clinical Use
Sodium phenylbutyrate is approved to treat urea cycle disorders in patients with liver enzyme deficiency.
Phase III 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
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].