Trends and Perspectives of Ruthenium Anticancer Compounds (Non-PDT)

Ruthenium is known as one of the most attractive metals for development of anticancer drugs. Three ruthenium(III) complexes were so far evaluated in clinical studies in cancer patients, with overall encouraging results. Specifically, NAMI-A, (im)[trans-RuIIICl4 (dmso)(Him)] (Him = imidazole), has been developed as an antimetastatic agent, but might require efficient tumor delivery strategies to raise its therapeutic index. KP1019, (ind)[trans-RuIIICl4 (Hind)2] (Hind = indazole), was originally developed with a focus on colorectal cancer, but clinical phase I data suggest broader activity. However, insufficient solubility for administration of a maximum tolerated dose prompted researchers to halt its development in favor of NKP-1339, Na[trans-RuIIICl4 (Hind)2]. For the latter, remarkable effects in carcinoid neuroendocrine tumors (and other solid tumors) were reported from a phase I trial. Based on quite different approaches, organometallic ruthenium(II) complexes are currently being studied preclinically, and keystone developments of these novel metallodrugs are discussed.