ruthenium-based transferrin targeting agent NKP-1339

A ruthenium-containing cancer agent targeting transferrin with potential antineoplastic activity. Upon intravenous administration, NKP-1339 (Ru3+) binds to transferrin (Tf) and is taken up via Tf receptors (TfR), which are overexpressed on cancer cells. Once inside the cell, NKP-1339 is released from Tf and is reduced, within the acidic environment of the endosomes, to its active form NKP-119 (Ru2+). In turn, the active form induces a redox reaction, thereby leading to the formation of reactive oxygen species (ROS) which inhibits GRP78 and SOD, endoplasmic reticulum-stress modulating molecules as well as BAG4 and ERK, program cell death regulating molecules. This eventually induces caspase-dependent apoptosis.