HK-4

HK-4 is a small-molecule inhibitor of Ketohexokinase-A (KHK-A) identified through structure-based virtual screening of the SPECS database. It demonstrates anti-tumor activity against hepatocellular carcinoma (HCC) by inhibiting cell proliferation, migration, and invasion. Mechanistically, HK-4 induces G1 phase arrest and apoptosis while suppressing the PI3K-AKT signaling pathway, specifically reducing the phosphorylation levels of AKT and mTOR. In preclinical studies, HK-4 exhibited half-maximal inhibitory concentrations (IC50) ranging from 22.54 µM to 23.91 µM across several HCC cell lines, including HepG2, PLC/PRF/5, and HuH7.