EPIC-0726

EPIC-0726 is a novel proteolysis-targeting chimera (PROTAC) designed to selectively induce the degradation of Polymerase I and transcript release factor (PTRF), also known as Cavin1. PTRF is a key protein in glioblastoma (GBM) that promotes chemoresistance to temozolomide (TMZ) by facilitating the secretion of small extracellular vesicles and the efflux of the drug. EPIC-0726 functions by recruiting the ubiquitin-proteasome system to degrade PTRF, which subsequently destabilizes RBX1, suppresses the ERK1/2 and AKT signaling pathways, and stabilizes the cell cycle inhibitor p21. Preclinical studies indicate that EPIC-0726 is more potent than small-molecule PTRF inhibitors (such as EPIC-1042) and significantly enhances the therapeutic efficacy of temozolomide in glioblastoma models by activating the PTRF-RBX1 regulatory axis.