ICG-001 Provides Cardioprotection Against Doxorubicin-Induced Cardiotoxicity and Enhances Cancer Cytotoxicity

Doxorubicin is effective against cancer but can cause doxorubicin-induced cardiotoxicity (DCT). Drug discovery efforts against DCT are hampered by the need to balance cardioprotection and cancer control. This study demonstrates that ICG-001 suppressed DCT in patient-derived human induced pluripotent stem cell-derived cardiomyocytes in vitro and in mice in vivo, comparable to conventional treatment, dexrazoxane. Unlike dexrazoxane, ICG-001 was cytotoxic to cancer cells. Mechanistically, ICG-001 protected the mitochondria in cardiomyocytes via DPR1 inhibition, but suppressed cancer by repressing Wnt signaling. These dual mechanisms underscore the potential of ICG-001 as an adjunct treatment to doxorubicin to improve its safety and efficacy.