SPA70 is a pregnane X receptor (PXR) antagonist (IC50 = 0.51 µM).1 It is selective for PXR over 10 additional nuclear receptors at concentrations greater than 5 µM, as well as over a panel of 384 kinases at 10 µM. SPA70 (0.1-10 µM) inhibits PXR activation induced by rifampicin in HEK293 cells expressing the human receptor. It also inhibits rifampicin-induced activity of the PXR target cytochrome P450 (CYP) isoform 3A4 (CYP3A4) in primary human hepatocytes. SPA70 (200 mg/kg) inhibits PXR agonist-induced CYP3A4-mediated metabolism of midazolam and paclitaxel in human PXR transgenic (hPXR-tg) mice.
1.Lin, W., Wang, Y.-M., Chai, S.C., et al.SPA70 is a potent antagonist of human pregnane X receptorNat. Commun.8(1)741(2017)