Guaianolide dimer KGA-1002 targets GRP94 and triggers unfolded protein response-associated degradation of SKP2/AKT axis as a novel antihepatoma agent

KGA-1002 was identified as a highly promising lead compound for antiHCC. Its mechanism involved triggering UPR-associated degradation and disrupting the GRP94-AKT interaction. KGA-1002 simultaneously induced apoptosis and ferroptosis in HCC cells through the GRP94/AKT/SKP2/P21 signaling axis.