NecroIr2 is an iridium(III) complex, serves as necroptosis inducers in Cisplatin (HY-17394)-resistant lung cancer cells (A549R). NecroIr2 selectively accumulates in mitochondria, leading to oxidative stress and loss of mitochondrial membrane potential (MMP). NecroIr2 activates receptor-interacting serine-threonine kinase 3 (RIPK3) and mixed lineage kinase domain-like pseudokinase (MLKL), and regulates CDK4 expression.In Vitro: NecroIr2 (2 μM; 1-2 d) exerts subcellular distribution over 90% accumulated in mitochondria in non-labelled A549R and CFSE labelled L02 cells.
NecroIr2 (1.5 μM and 3 μM; 24 h) results ROS generation increasing and loss of mitochondrial membrane potential.
NecroIr2 (1.5 μM and 3 μM; 24 h) activates necroptosis proteins, increases the phosphorylation of RIPK1 and RIPK3.
NecroIr2 (0.75 μM and 1.5 μM; 24 h) induces necroptosis by arresting cell cycle at G0/G1.
NecroIr2 (0.375-1.5 μM; 24 h) inhibits A549R cells proliferation.