MI891 

MI891 is a highly selective PXR antagonist (IC₅₀ = 3.76 μM, K_d = 1.7 μM) and inverse agonist (IC₅₀ = 6.1 μM). MI891 selectively disrupts the interaction between PXR and its coactivator SRC1. MI891 effectively inhibits Rifampicin (HY-B0272)-induced PXR activation. MI891 is useful for the study of metabolic diseases and other diseases^[1].

MI891 (0-10 μM) abrogates PXR activation by Rifampicin (HY-B0272) and displays antagonistic activity with an IC₅₀ of 378 nM^[1].
MI891 (0-20 μM, 48 h) suppresses both rifampicin-induced and basal (constitutive) CYP3A4 mRNA expression in HepaRG cells^[1].
MI891 (1-10 μM) disrupts the wt-PXR-LBD/SRC1-VP16 interaction, does not activate the obstructed mutated PXR LBD in wild-type (wt-PXR LBD) or triple mutant (S208W/S247W/C284W) in HepG2 cells^[1].
MI891 (48 h) shows no binding activity (EC₅₀ > 10 μM) in wild-type CAR; requires high concentrations to activate CAR (EC₅₀ = 137 μM) and has no significant activation of either CARwt or CAR3 variant in human CARwt and CAR3 in HepG2 cells^[1].
MI891 (10 μM, 48 h) exhibits selective antagonism and inverse agonism on hPXR, but has no agonistic or antagonistic activities of MI891 on human VDR, FXR, LXRβ, LXRα, PPARα, PPARγ, AhR, or ERα/β receptors^[1].
MI891 (24 h) demonstrates no effects on viability in various cell lines (up to 30 μM), including COS-1, HepG2, and HK-2^[1].
MI891 (5-10 μM, 48 h) suppresses the expression of CYP3A4, CYP7A1, HMGCS2, PCK1, and MKI67 mRNA in primary human hepatocytes^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

499.30

C₂₃H₁₄Cl₂F₂N₆O

2530027-77-9

O=C(N)C1=CC(CN2N=NC(C3=C(C4=CC=C(Cl)C=C4)N=C5C(F)=CC(F)=CN53)=C2)=CC=C1Cl

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Kamaraj R, et al. Discovery of PXR Antagonist MI891 and PXR Degrader MI1013 and Their Roles in Hepatic Gene Regulation. J Med Chem. 2025 Jul 24;68(14):14271-14299.  [Content Brief]