Phenylbutyric Acid: A Comprehensive Review of its Pharmacology, Therapeutic Applications, and Clinical Profile

1. Introduction to Phenylbutyric Acid

1.1. Overview and Significance

Phenylbutyric acid, a derivative of the short-chain fatty acid butyric acid, is a pharmacologically active compound with established and emerging therapeutic applications.[1] It is recognized as being naturally produced by the fermentation processes of colonic bacteria.[1] The primary clinical significance of phenylbutyric acid lies in its role as an adjunctive therapy for the chronic management of urea cycle disorders (UCDs), a group of rare genetic metabolic conditions characterized by the inability to effectively eliminate waste nitrogen.[1] Beyond this well-defined indication, phenylbutyric acid exhibits a broader spectrum of biological activities. These include functioning as a histone deacetylase (HDAC) inhibitor and as a chemical chaperone, properties that form the basis for its investigation in a variety of other pathological states.[1] The diverse pharmacological profile of phenylbutyric acid suggests its potential utility extends beyond its primary metabolic role, encompassing inflammatory conditions, certain malignancies, and neurodegenerative disorders.

1.2. Initial DrugBank and User-Provided Information

The compound under review is Phenylbutyric acid, identified in the DrugBank database with the accession number DB06819.[1] Its Chemical Abstracts Service (CAS) registry number is 1821-12-1.[2] Phenylbutyric acid is classified as a Small Molecule drug.[1]

Its principal approved use is as an adjunctive therapeutic agent for the chronic management of UCDs. This includes enzyme deficiencies presenting in the neonatal period (neonatal-onset deficiency) as well as those manifesting later in life (late-onset disease) in individuals with a prior history of hyperammonemic encephalopathy.[1]