4-Phenylbutyric acid (4-PBA) is a multifunctional small molecule acting as a chemical chaperone to alleviate endoplasmic reticulum (ER) stress, an HDAC inhibitor (HDACi), and an ammonia scavenger used for urea cycle disorders. It stabilizes protein conformation, reduces misfolding, and has potential in treating neurodegenerative and metabolic diseases.

Key Derivatives and Related Compounds:

4-Phenylbutyramide: A derivative often investigated for increased metabolic stability and potency as a chaperone.

3-Phenylpropionic acid (3-PPA): A structurally related, shorter-chain analogue with similar, albeit usually weaker, chemical chaperone properties.

Phenylacetate: The direct metabolite of 4-PBA, which also acts as an ammonia scavenger.

4-phenylbutyrate derivatives: Various synthetic derivatives have been developed to enhance the ability of 4-PBA to prevent protein misfolding, particularly for conditions like ALS.

Key Functions
Chemical Chaperone: Interacts with hydrophobic segments of unfolded proteins to prevent aggregation and reduce ER stress.

HDAC Inhibitor (HDACi): Increases histone acetylation to modulate gene expression, often inhibiting cancer cell proliferation.

Ammonia Scavenger: Metabolized to phenylacetate, which conjugates with glutamine to form phenylacetylglutamine, which is then excreted in urine, bypassing the urea cycle.

4-PBA is also known for reducing lipotoxicity in hepatoma cells and protecting against cardiac ischemia-reperfusion injury.