摘要Lung cancer takes the lead in terms of global cancer incidence and mortality rates.5'-adenosine monophosphate(AMP)-activated protein kinase(AMPK)serves as a universally conserved energy sensor throughout evolution checkpoint that orchestrates energy balance and metabolic homeostasis.However,AMPK activation has a complex,dual function in both the onset and advancement of lung cancer.Despite its protumorigenic effects,targeting AMPK with inhibitors to suppress cancer progression remains a critical area of research.An innovative high-content screening platform integrating small-molecule microarrays(SMMs)with oblique-incidence reflectivity difference(OI-RD)optical detection was estab-lished for AMPK inhibitor discovery.Alterations in the interfacial refractive index revealed that Ribavirin,an antiviral drug,has a high affinity for AMPK.Ribavirin binds directly to AMPK,suppressing its acti-vation in mouse and human cells.By inhibiting AMPK phosphorylation,Ribavirin affects the downstream phosphorylation of mechanistic target of rapamycin complex 1(mTORC1)and eukaryotic translation initiation factor 4E(eIF4E)-binding protein 1(4EBP1),thereby regulating tumor cell proliferation and apoptosis.These results identify Ribavirin as a new AMPK inhibitor with potential utility in lung cancer therapy.