KP1019

KP1019, or indazole trans-[tetrachlorobis(1H-indazole)ruthenate(III)], is one of four ruthenium anti-cancer drugs to enter into phase I clinical trials, the others being BOLD-100, NAMI-A and TLD-1433.

Research into ruthenium-based drugs has provided novel alternatives for platinum-based chemotherapeutics such as Cisplatin and its derivatives.

[1] KP1019 has an octahedral structure with two trans N-donor indazole and four chloride ligands in the equatorial plane.

The Ru-Cl bonds are labile and KP1019 readily exchanges its chloro ligands in the presence of water.

The resulting solid is collected by filtration and its purity is evaluate by UV-visible spectroscopy, elemental analysis, and determination of reduction potential.

An increase in Ru (III) reduction potential positively correlates with the complex's antiproliferative activity.

This protein and its receptors are overexpressed in cancer cells owing to their increased demand for iron, and it is believed that Tf transport is the reason ruthenium compounds accumulate in tumors.

The intracellular release requires a significant increase in pH due to the high binding affinity.

In tumor cells, the drug induces 15-fold lower interstrand DNA cross-linking efficiency than cisplatin.

The interaction of KP1019 and its imidazole-containing analogue KP418 with DNA increases in the hypoxic environment that tumor cells are subject to.

Human Transferrin (Tf) PDB: 2HAU
Human Serum Albumin (HSA) PDB: 1AO6