ironomycin

Ironomycin (also known as AM5) is a synthetic small molecule designed to target iron metabolism in cancer cells, specifically acute myeloid leukemia (AML). It functions by sequestering iron within lysosomes, which prevents its translocation to the mitochondria. This mitochondrial iron deprivation disrupts the tricarboxylic acid (TCA) cycle and oxidative respiration, leading to a mitochondrial stress response and a non-canonical form of cell death that is dependent on the pro-apoptotic proteins BAX and BAK. Preclinical studies have demonstrated that ironomycin is effective as a monotherapy and highly synergistic with the BCL2 inhibitor venetoclax, even in venetoclax-resistant AML models.