4-ethylphenyl sulfate (4-EPS)

4-ethylphenyl sulfate (4-EPS) is a gut-microbiome-derived metabolite produced through the microbial fermentation of dietary tyrosine and subsequent host sulfation in the liver (Needham et al., 2022). It is classified as a uremic toxin and has emerged as a critical mediator in the gut-brain axis, particularly in the context of neurodevelopmental disorders (Hsiao et al., 2013; Frontiers, 2023). Research indicates that 4-EPS can cross the blood-brain barrier and influence brain function by impairing the maturation of oligodendrocytes and reducing myelination in regions such as the corpus callosum (Needham et al., 2022). These physiological changes are linked to the induction of anxiety-like behaviors, and elevated levels of 4-EPS have been observed in a subset of individuals with autism spectrum disorder (ASD) (Campbell et al., 2022). Beyond its neuroactive properties, 4-EPS has been shown to interact with the angiotensin II type 1 receptor (AT1R), potentially modulating blood pressure and cardiovascular health (bioRxiv, 2025). It also exhibits selective anticancer activity in colorectal cancer cells by interacting with histone deacetylase (HDAC) isoforms (J Med Chem, 2025). Due to its role in promoting anxiety and its association with ASD, 4-EPS is a primary therapeutic target for sequestration strategies. The investigational drug AB-2004 is an oral adsorbent designed to bind 4-EPS in the gastrointestinal tract, preventing its systemic absorption and thereby reducing its impact on the central nervous system (Campbell et al., 2022; Axial Therapeutics).

Other names

4-ethylphenylsulfatep-ethylphenyl sulfate4-ethylphenyl hydrogen sulfate4-ethylphenylsulfuric acid

Sequestration in the gastrointestinal tract using oral adsorbents to prevent systemic absorption and subsequent neurotoxicity.