Nur77 modulator 1 is a good Nur77 binder (KD = 3.58 μM). Nur77 modulator 1 up-regulates Nur77 expression, mediates sub-cellular localization of Nur77, induces Nur77-dependent ER stress and autophagy, and results in cell apoptosis. Nur77 modulator 1 shows anti-hepatoma activity.

Nur77 modulator 1 (10g, 0-20 μM) demonstrates potent, broad-spectrum antiproliferative effects against the hepatoma cell lines HepG2, QGY-7703, and SMMC-7721, with minimal cytotoxicity towards LO2 normal human liver cells. It specifically enhances Nur77 expression in a dose-dependent manner and induces Nur77-dependent apoptosis at 2.0 μM. Additionally, at this concentration, it elevates LC3-II and Beclin1 protein levels, suggesting autophagy activation; however, it does not promote p62 degradation, indicating incomplete autophagy. In cell viability assays, the compound exhibited IC50 values of 0.6 μM, 0.89 μM, and 1.40 μM for HepG2, QGY-7703, SMMC-7721, respectively, and over 20 μM for LO2 cells. It effectively reduced cell viability over time and induced cellular morphological changes, including shrinkage and vesicle accumulation.

Nur77 modulator 1 (10g, 10 and 20 mg/kg/day) exhibits significant anti-tumor activity in mouse hepatoma HepG2 xenograft with good tolerability [1]. Animal Model: Nude mouse hepatoma HepG2 xenograft [1]. Dosage: 10 and 20 mg/kg/day. Administration: IP, once every day for 15 days. Result: Lead to substantial suppression of tumor growth. The tumor growth inhibition (TGI) values at doses of 10mg/kg/day and 20 mg/kg/day were 36.74 % and 62.38 %, respectively. Exhibited almost no influence on the body weight of experimental mice. These results indicate that Nur77 modulator 1 has the potential to be developed as a novel Nur77-targeting anti-hepatoma drug.