In this study, we found a novel indozole derivative TYM-3–98 that can efficiently inhibit PI3Kδ, which triggeres ferroptosis in CRC via the PI3K–AKT–mTOR-SREBP1 signaling pathway and suppresses the growth of KRAS-mutant CRC both in vitro and in vivo. Here, MTOR is linked to colorectal carcinoma.