MI1013 

MI1013 is a PROTAC PXR degrader (DC₅₀ = 89 nM, D_max = 82%). MI1013 degrades PXR in human hepatocellular carcinoma RG cells (HepaRG). MI1013 specifically and safely regulates CYP3A4 promoter activity through PXR degradation. MI1013 affects several key genes involved in sulfate conjugation (e.g., SULT1E1), bile acid synthesis (CYP7A1), gluconeogenesis (PCK1), ketone synthesis (HMGCS20), and hepatocyte proliferation (MKI67). (Pink: PXR ligand 3: HY-175267, Blue: Pomalidomide-propargyl ligand: HY-W410002, Pink + Black: PXR ligand-Linker Conjugate 1: HY-175268)^[1].

MI1013 (0.01-10 μM, 0-96 h) induces degradation of PXR, but does not degrade RXRα and GSPT1 in HepaRG and MOLT4 cells^[1].
MI1013 (1-10 μM, 24 h) inhibits PXR and PXR-HiBiT degradation, does not exhibit agonistic activity at concentrations up to 10 μM in HepaRG cells using the CYP3A4 gene promoter luciferase construct^[1].
MI1013 is less competitive in binding to PXR LBD^[1].
MI1013 (24 h) is nontoxic up to a concentration of 100 μM in HepaRG , HK-2, COS-1, and HepG2 cells^[1].
MI1013 (2 μM, 24 h) effectively modulates PXR activity, allowing CAR to regain its function in HepaRG cells^[1].
MI1013 (2 μM, 24 h) down-regulates the mRNA levels of CYP3A4, SULT1E1 and SULT1B1 encoding sulfotransferases, CYP7B1, NR0B2, and CYP7A1, and up-regulates the mRNA level of UGT1A1 in HepaRG Cells and Human Hepatocytes^[1].

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

914.94

C₄₂H₄₆N₁₀O₁₂S

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• [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]