Identification of an Iridium(III)-Based Inhibitor of Tumor Necrosis Factor-α

The novel iridium(III) complex 1 was verified as a potent inhibitor of the TNF-α–TNFR protein–protein interaction in vitro and in cellulo. The iridium(III) center plays a critical role in organizing the structure of the bioactive metal complex, as the isolated ligands were found to be completely inactive. Both iridium enantiomers inhibited TNF-α-induced NF-κB activity and TNF-α–TNFR binding. 1 represents a promising scaffold for the further development of more potent organometallic TNF-α inhibitors.