Indoxyl Sulfate (potassium salt)

Indoxyl Sulfate (potassium salt) (CAS No.: 2642-37-7) is an endogenous uremic toxin derived from dietary tryptophan metabolism, produced by intestinal microbiota and subsequently sulfated in the liver before entering systemic circulation. It is widely recognized as a protein-bound metabolite that accumulates in patients with impaired renal function, particularly in chronic kidney disease, where it contributes to disease progression through the induction of oxidative stress and proinflammatory signaling. Mechanistically, indoxyl sulfate functions as a potent agonist of the aryl hydrocarbon receptor (AhR), with activity observed in the nanomolar range in reporter assays, and modulates multiple downstream pathways, including activation of NF-κB and enhancement of the p53–TGF-β1–Smad3 signaling axis, thereby promoting profibrotic responses in renal proximal tubular cells. In addition, it inhibits organic anion transporters such as OAT1 and OAT3 at low to mid micromolar concentrations and elevates reactive oxygen species and nitric oxide production in immune cells, reflecting its role in systemic oxidative stress and inflammation. In vivo, elevated levels are associated with worsened renal function markers in experimental models of kidney injury. This compound is commonly used in biomedical research to investigate uremic toxicity, kidney disease mechanisms, transporter-mediated drug interactions, and AhR-related signaling, with experimental concentrations or dosing regimens varying depending on specific in vitro or in vivo study designs.