Neurological and hematological safety profiles of GSK-3β inhibitors: insights from multi-database pharmacovigilance and experimental validation.

چکیده اصلی

BACKGROUND: Glycogen synthase kinase 3 beta (GSK-3β) inhibitors have received substantial attention for their therapeutic potential; however, their systemic safety profile remains incompletely characterized. OBJECTIVE: This study characterized the research landscape and exploratory safety-reporting signals associated with agents with reported GSK-3β activity by integrating bibliometric analysis, pharmacovigilance, and preliminary experimental assessment. METHODS: A multi-layered framework included bibliometric analysis, disproportionality analyses of FAERS, JADER, and CVARD reports, and transcriptomic profiling. SH-SY5Y cells were treated with 9-ING-41 (1 μM, 24 h); cell viability, qRT-PCR, and DCFH-DA-based intracellular oxidative-stress measurements were assessed. RESULTS: Bibliometric analysis showed sustained growth in GSK-3β-related research. Pharmacovigilance identified neurological and hematologic disproportionality signals across 27 System Organ Classes. In SH-SY5Y cells, 9-ING-41 was associated with modest changes in neuronal-function, inflammatory-response, and GSK-3β/Wnt-pathway transcripts, increased DCFH-DA fluorescence, and high cell viability. These cell-based observations are preliminary and do not establish clinical causality. CONCLUSION: The literature-derived study-drug panel showed exploratory neurological and hematologic reporting signals. Cross-database recurrence can prioritize hypotheses, whereas pharmacological heterogeneity and the limitations of spontaneous reporting require cautious interpretation. The SH-SY5Y experiments provide preliminary biological plausibility only.

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