Biochem/physiol Actions

Elesclomol (STA-4783) is a copper (II)-chelating malonohydrazide derivative that exerts its in vitro and in vivo anticancer efficacy via reactive oxygen species (ROS)/oxidative stress & apoptosis induction in a Cu(II)-dependent manner (GI₅₀ = 12 nM without vs. 129 nM with Cu²⁺ removal by TRIEN in K562 culture; typical conc. range 0.1-2 µM in cultures). Elesclomol chelates extracellular Cu(II) for mitochondria delivery, where upon Cu²⁺ reduction (to Cu⁺) & ROS generation, copper-free elesclomol then exits cells for continual Cu(II) shuttling and accumulation in mitochondria. In addition to Cu²⁺, elesclomol can also chelate Co²⁺ and Ni²⁺, but not Fe³⁺ or Zn²⁺.