MI891 is a highly selective PXR antagonist (IC50= 3.76 μM, Kd= 1.7 μM) and inverse agonist (IC50= 6.1 μM). It selectively disrupts the interaction between PXR and its coactivator SRC1. MI891 effectively inhibits Rifampicin-induced PXR activation and can be utilized in research on metabolic and other diseases.

MI891 effectively inhibits Rifampicin-induced activation of PXR, displaying antagonistic activity with an IC50 of 378 nM. At concentrations of 0-20 μM over 48 hours, MI891 suppresses both Rifampicin-induced and constitutive (basal) CYP3A4 mRNA expression in HepaRG cells. In HepG2 cells, MI891 (1-10 μM) disrupts the interaction between wt-PXR-LBD and SRC1-VP16 without activating the wild-type (wt-PXR LBD) or the triple-mutant (S208W/S247W/C284W) PXR LBD. It shows no binding activity to wild-type CAR in human CARwt and HepG2 cells (EC50 > 10 μM); high concentrations are necessary to activate CAR, with an EC50 of 137 μM, in human CARwt or CAR3 variants without significant activation of CAR3. MI891 (10 μM, 48 hours) demonstrates selective antagonistic and inverse agonistic effects on hPXR without agonism or antagonism effects on human VDR, FXR, LXRβ, LXRα, PPARα, PPARγ, AhR, or ERα/β receptors. It does not affect the viability of various cell lines, such as COS-1, HepG2, and HK-2, at concentrations up to 30 μM over 24 hours. Additionally, MI891 (5-10 μM, 48 hours) inhibits the expression of CYP3A4, CYP7A1, HMGCS2, PCK1, and MKI67 mRNA in primary human hepatocytes.