SU212 is a podophyllotoxin-derived ENO1 inhibitor and AMPK activator. It selectively induces oxidative phosphorylation in cells, reduces glycolytic activity and glucose uptake in tumor cells, and directly binds ENO1 without affecting pathways in normal cells. SU212 induces apoptosis and facilitates ENO1 degradation via proteasomal and autophagic pathways without inhibiting its catalytic activity. It activates AMPK independently of energy stress and without being affected by glucose or insulin levels, resulting in M phase arrest and apoptosis in triple-negative breast cancer (TNBC) cells, demonstrating potent in vitro antitumor activity. Additionally, SU212 inhibits tumor growth and metastasis in syngeneic, xenograft, and diabetic mouse models, showing excellent safety profiles. This compound can be utilized in research on TNBC, diabetes, and fatty liver disease.
