Keap1-Nrf2-IN-4, a powerful neddylation inhibitor, demonstrates significant anti-proliferation activity against MGC-803 cells (IC50 = 2.55 μM), effectively impeding their migration and inducing apoptosis. Additionally, it effectively inhibits tumor growth while exhibiting minimal toxicity [1].

Keap1-Nrf2-IN-4 (compound 4g) (72 h) shows anti-proliferation activity (IC 50 s of 2.55, 3.88, 3.74, 2.89 μM in MGC-803, MCF-7, A549, HepG-2 cells, respectively) [1]. Keap1-Nrf2-IN-4 inhibits neddylation of cullin1, cullin3, cullin5 [1]. Keap1-Nrf2-IN-4 blocks the migration ability of MGC-803 without cell cycle arrest [1]. Keap1-Nrf2-IN-4 (24, 48 h) induces apoptosis of MGC-803 and HGC-27 cells in concentration- and time-dependent manners [1]. Cell Proliferation Assay [1] Cell Line: MGC-803, MCF-7, A549, HepG-2 cells Concentration: Incubation Time: 72 h Result: Showed anti-proliferation activity (IC 50 of 2.55, 3.88, 3.74, 2.89 μM in MGC-803, MCF-7, A549, HepG-2 cells, respectively). Apoptosis Analysis [1] Cell Line: MGC-803, HGC-27 cells Concentration: 2.5, 5, 7.5 μM for MGC-803 cells; 3, 6, 9 μM for HGC-27 cells Incubation Time: 24 h, 48 h Result: Induced apoptosis of MGC-803 and HGC-27 cells in concentration- and time-dependent manners.

Keap1-Nrf2-IN-4 (50, 100 mg/kg; i.g.; per day for 21 days) exhibits antitumor activity on xenograft model without obvious side effect [1]. Animal Model: 5-6 weeks, 18-20 g, NOD SCID mice (xenograft tumor model) [1] Dosage: 50, 100 mg/kg Administration: i.g.; per day, 21 days Result: Exihibited good antitumor activity on xenograft model without obvious side effect.