This research demonstrates that [68Ga]Ga-DOTA-FZ-P5R enables rapid imaging of PRMT5-positive tumors. The probe has significant potential to enable individualized and precise diagnosis in patients with PRMT5-positive tumors, define an optimal treatment window, assess therapeutic efficacy, and serve as a predictive imaging modality for tumor resistance.
Analysis of consensus QSAR models identified two highly active PRMT5 inhibitor candidates (CHEMBL4539612 and CHEMBL4577464), with high affinity for binding (- 13.5 to - 13.7 kcal/mol) to the PRMT5 active site and interactions similar to those of the known clinical PRMT5 inhibitor ONAMETOSTAT...Network pharmacology analysis indicated that PRMT5 and its interacting partners are mainly associated with histone arginine methylation and spliceosomal assembly, processes that are frequently dysregulated in MTAP-deficient cancers. These findings suggest CHEMBL4539612 and CHEMBL4577464 as promising scaffolds for the development of selective PRMT5 inhibitors in epigenetic cancer therapy.