FKK6 (Felix Kopp Kortagere 6) is a specific human pregnane X receptor (hPXR) agonist with IC50 of 1.56 uM in a cell‐free competitive hPXR TR‐FRET‐binding assays.
FKK6 did not significantly activate mouse PXR, did not activate AhR and several other related xenobiotic receptors, as well as a broad array of kinase enzymes.
FKK6 induces robust expression of PXR target genes in intestinal cell lines (LS180, LS174T), also enhances both CYP3A4 and MDR1 promoter occupancy in cells.
FKK6 inhibited NF‐κB activation in a PXR‐dependent manner in intestinal cell lines (LS180, LS174T), inhibited cytokine and salmonella infection‐induced NF‐κB nuclear translocation in Caco‐2 cells and iPSC‐derived human intestinal organoids.
FKK6 induced PXR target gene cyp3a11 in mice expressing the human PXR transgene, but not in conventional wild‐type mice or pxr −/− mice, abrogated dextran sulfate sodium‐induced colitis in mice expressing the human PXR gene.