Lu_2026_Future.Med.Chem__1

OBJECTIVE: This study aims to investigate whether butyrylcholinesterase (BChE) inhibitor QY-54 can be used to treat glioblastoma (GBM) and exert a neuroprotective profile. METHODS: At the cellular level, the effects of QY-54 on the proliferation, invasion, and migration of GBM cells from different species were investigated. At the animal level, the safety of QY-54 in normal mice, its anti-tumor effects in GBM mice, and its effects on cognition protective function were examined. RESULTS: At the cellular level, QY-54 exhibited significant inhibitory effects on the proliferation, migration, and invasion of GBM cells derived from different species. At the animal level, QY-54 showed low toxicity in normal mice. Moreover, it significantly inhibited GBM tumor growth, promoted tumor cell apoptosis, suppressed neuroinflammation, protected neurons, and improved the general condition and cognitive function of GBM mice. In Western blot experiments, QY-54 upregulated c-jun N-terminal kinase (JNK) levels to exert an inhibitory effect on glioma. CONCLUSION: QY-54 exhibits dual effects of anti-glioblastoma and cognitive improvement, by inhibiting BChE and activating the JNK signaling pathway. QY-54 is a highly promising drug for the treatment of glioblastoma with neuroprotective profile.