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Ruthenium – Anti-Cancer Drugs

Ruthenium – Anti-Cancer Drugs

Ruthenium anti-cancer drugs are coordination complexes of ruthenium complexes that have anticancer properties. They promise to provide alternatives to platinum-based drugs for anticancer therapy. No ruthenium anti-cancer drug has been commercialized.

The leading ruthenium-based candidates are NAMI-A and KP1019. The first one to enter was NAMI-A. More ruthenium drugs are still under development. Ruthenium complexes as anticancer drugs are almost always designed to mimic platinum drugs, for targeting DNA.

Current Ruthenium anti-cancer drugs


Chemical structure of imidazolium trans-imidazoledimethylsulfoxidetetrachloro-ruthenate (NAMI-A)

NAMI {Na[trans-RuCl4](DMSO)(imida)]} and NAMI-A {H2Im[trans-RuCl4(DMSO)HIm[imidH] are the most-stable ruthenium-based anti-cancer drugs.[5] NAMI-A is considered a pro-drug and is inactive at physiological pH of 7.4.[1] Cancer cells generally contain a lower oxygen concentration as well as higher levels of glutathione and a lower pH than normal tissues creating a reducing environment. Upon entering cancer cells NAMI-A is activated by the reduction of Ru(III) to Ru(II) to form the active anti-cancer agent.


KP1019, a salt of trans-tetrachlorobis(indazole)ruthenate(III), has entered into clinical trials.[9] KP1019 has an octahedral structure with two trans N-donor indazole and four chloride ligands in the equatorial plane.[10][11][12] It has a low solubility in water, which makes it difficult to transport in the bloodstream. Instead KP1339[clarification needed] is used as a preparation of KP1019 in clinical trials, since it has a better solubility as a sodium salt.[12]

Proteins and other N-donors are good binding partners for KP1019.

Especially transferrin and albumin are good binding partners.[16] The overall method of action for KP1019 needs to be supported further.

Tumor cells have a high requirement of iron, which results in a large concentration of transferrin. Ru(III) complexes bind to transferrin and proposed to interfere with iron uptake.


RAPTA compounds are ruthenium–arene complexes bearing the 1,3,5-triaza-7-phosphatricyclo-[]decane ligand. The complex has a piano stool geometry. The PTA ligand confers water solubility, and the two chloride ligands are labile. RAPTA compounds have low general toxicity that apparently reduces the side-effects associated with chemotherapy.


Ruthenium diamine complexes are of interest as potential anticancer drugs.[20][21] RAED compounds are ruthenium–arene complexes bearing the 1,2-ethylenediamine ligand.

The ruthenium diamine complexes form adducts with guanine. Methylation or substitution on en-NH, which prevent the hydrogen bonding, can lead to the loss of cytotoxic activity of the complex toward cancer cell. The ethylenediamine ligand suppresses reactions of the complex with amino acid residues. The Ru(II) complexes have a higher affinity to DNA in the presence of protein than the Ru(III) compounds, such as NAMI-A.