elesclomol analog

Elesclomol analog is a soluble, copper-complexed derivative of the ionophore elesclomol, specifically engineered to overcome the solubility and pharmacokinetic limitations that hindered the clinical success of the parent compound. It functions by transporting copper into the mitochondria, where it triggers cuproptosis—a form of regulated cell death characterized by the lipoylation and aggregation of mitochondrial proteins, leading to proteotoxic stress and metabolic failure. This process is primarily mediated by ferredoxin 1 (FDX1), which reduces copper and regulates protein lipoylation. The analog shows enhanced antitumor efficacy and reduced systemic toxicity in preclinical models compared to the original elesclomol. Its activity is further regulated by the coupling of FDX1 with mitochondrial cytochrome P450 enzymes (CYP11A1 and CYP27A1), which can act as resistance factors by sequestering FDX1 activity, a relationship that may also protect FDX1-high organs like the adrenal gland and kidney from toxicity.

Other names

soluble elesclomol analogcopper elesclomol analogsoluble copper ES analog