FU-4046

FU-4046 is a potent and selective small molecule aryl hydrocarbon receptor (AhR) antagonist. Developed by researchers at Aix-Marseille University, INSERM, and INRAE, FU-4046 is designed to inhibit AhR activation triggered by tryptophan-derived uremic toxins, such as indoxyl sulfate, which accumulate in patients with chronic kidney disease (CKD). In vitro studies have demonstrated that FU-4046 can strongly suppress the AhR activation potential of serum from hemodialysis patients and reduce the upregulation of both AhR target genes (such as CYP1A1, CYP1B1, and AHRR) and inflammatory genes (such as F3, PTGS2, CCL2, CXCL8, and IL6) in endothelial cells. This therapeutic approach aims to mitigate endothelial thrombo-inflammation and associated cardiovascular complications in patients with end-stage kidney disease (ESKD).