Cu4B

Cu4B is a copper(II) complex based on a pyridine hydrazone ligand. It is designed as a multifunctional therapeutic agent that induces immunogenic cell death (ICD) in hepatocellular carcinoma (HCC) by simultaneously activating cuproptosis, apoptosis, and chemodynamic therapy. Cu4B depletes intracellular glutathione (GSH) and catalyzes the conversion of hydrogen peroxide into hydroxyl radicals via a Fenton-like reaction, leading to oxidative stress and mitochondrial damage. It upregulates dihydrolipoamide S-acetyltransferase (DLAT) and downregulates lipoic acid synthase (LIAS) and ferredoxin 1 (FDX1), triggering cuproptosis. In preclinical models of HCC, Cu4B has demonstrated potent cytotoxicity and antitumor immune responses, which are further enhanced when combined with the HIF-1α inhibitor PX-478.