4-Aminophenylacetic acid (4-APAA)

4-Aminophenylacetic acid (4-APAA) is a small molecule immunomodulator and a key metabolite of the antirheumatic drug Actarit (4-acetylaminophenylacetic acid). It is primarily recognized for its ability to modulate immune responses by suppressing the production of pro-inflammatory cytokines such as interleukin-2 (IL-2), interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha). Recent research has identified Carbonic Anhydrase II (CAII) as a direct molecular target of 4-APAA, where it acts as a submicromolar inhibitor. Additionally, 4-APAA functions as a peptidomimetic that interacts with the proton-coupled oligopeptide transporter PepT1 (SLC15A1), influencing intestinal peptide sensing and glucose homeostasis. Therapeutically, 4-APAA is utilized in the treatment of rheumatoid arthritis and is being developed as a component of azo-bonded prodrugs (e.g., INN-108) for the targeted treatment of ulcerative colitis and other inflammatory bowel diseases. Its mechanism involves the regulation of T-cell activation and macrophage function, contributing to its disease-modifying properties in autoimmune conditions.

Other names

p-Aminophenylacetic acid4-APAActarit metaboliteDesacetylactarit

Inhibition of Carbonic Anhydrase II (CAII), modulation of IL-2 and TNF-alpha production, interaction with PepT1 (SLC15A1) transporter, and suppression of T-cell activation.