Nur77 modulator 1 is an effective Nur77 binder (KD = 3.58 μM) that up-regulates Nur77 expression, mediates its sub-cellular localization, induces Nur77-dependent ER stress and autophagy, and leads to cell apoptosis, demonstrating anti-hepatoma activity.

Nur77:3.58 μM (KD)

Nur77 modulator 1 (10g, 0-20 μM) exhibits potent, broad-spectrum antiproliferative effects against hepatoma cell lines (HepG2, QGY-7703, SMMC-7721) with minimal cytotoxicity towards LO2 normal human liver cells. It enhances Nur77 expression in a dose-dependent manner and induces Nur77-dependent apoptosis at 2.0 μM, elevating LC3-II and Beclin1 protein levels to suggest autophagy activation without promoting p62 degradation, indicating incomplete autophagy. The compound shows IC50 values of 0.6 μM, 0.89 μM, and 1.40 μM for HepG2, QGY-7703, and SMMC-7721, respectively, and over 20 μM for LO2 cells; it effectively reduces cell viability over time and induces morphological changes, including shrinkage and vesicle accumulation.

Nur77 modulator 1 (10g, 10 and 20 mg/kg/day) shows significant anti-tumor activity with good tolerability in a nude mouse hepatoma HepG2 xenograft model [1]. Administered intraperitoneally once daily for 15 days, it leads to substantial tumor growth suppression, with tumor growth inhibition values of 36.74 % at 10 mg/kg/day and 62.38 % at 20 mg/kg/day, and almost no impact on body weight, indicating potential as a novel Nur77-targeting anti-hepatoma drug.