Structure-activity relationships for ruthenium and osmium anticancer agents - towards clinical development.

Title Structure-activity relationships for ruthenium and osmium anticancer agents - towards clinical development.
Authors S.M. Meier-Menches; C. Gerner; W. Berger; C.G. Hartinger; B.K. Keppler
Journal Chem Soc Rev
DOI 10.1039/c7cs00332c
Abstract

Anticancer metallodrugs based on ruthenium and osmium are among the most investigated and advanced non-platinum metallodrugs. Inorganic drug discovery with these agents has undergone considerable advances over the past two decades and has currently two representatives in active clinical trials. As many ruthenium and osmium metallodrugs are prodrugs, a key question to be addressed is how the molecular reactivity of such metal-based therapeutics dictates the selectivity and the type of interaction with molecular targets. Within this frame, this review introduces the field by the examples of the most advanced ruthenium lead structures. Then, global structure-activity relationships are discussed for ruthenium and osmium metallodrugs with respect to in vitro antiproliferative/cytotoxic activity and in vivo tumor-inhibiting properties, as well as pharmacokinetics. Determining and validating global mechanisms of action and molecular targets are still major current challenges. Moreover, significant efforts must be invested in screening in vivo tumor models that mimic human pathophysiology to increase the predictability for successful preclinical and clinical development of ruthenium and osmium metallodrugs.

Citation S.M. Meier-Menches; C. Gerner; W. Berger; C.G. Hartinger; B.K. Keppler.Structure-activity relationships for ruthenium and osmium anticancer agents - towards clinical development.. Chem Soc Rev. 2017. doi:10.1039/c7cs00332c

Related Elements

Osmium

See more Osmium products. Osmium (atomic symbol: Os, atomic number: 76) is a Block D, Group 8, Period 6 element with an atomic weight of 190.23. Osmium Bohr ModelThe number of electrons in each of osmium's shells is [2, 8, 18, 32, 14, 2] and its electron configuration is [Xe] 4f14 5d6 6s2. The osmium atom has a radius of 135 pm and a Van der Waals radius of 216 pm. Osmium was discovered and first isolated by Smithson Tennant in 1803. Elemental OsmiumIn its elemental form, osmium has a silvery blue cast apperance. Osmium has the highest melting point and the lowest vapor pressure of any of the platinum group of metals it is also the densest naturally ocurring element. Osmium is the least abundant stable element in the earth's crust. It is found in the alloys osmiridium and iridiosmium and as a free element. The origin of the name Osmium comes from the Greek word osme, meaning a smell or odor.

Ruthenium

See more Ruthenium products. Ruthenium (atomic symbol: Ru, atomic number: 44) is a Block D, Group 8, Period 5 element with an atomic weight of 101.07. Ruthenium Bohr ModelThe number of electrons in each of ruthenium's shells is [2, 8, 18, 15, 1] and its electron configuration is [Kr] 4d7 5s1. The ruthenium atom has a radius of 134 pm and a Van der Waals radius of 207 pm. Ruthenium was discovered by Jędrzej Śniadecki in 1807. It was first recognized as a distinct element by Karl Ernst Claus in 1844. Elemental RutheniumIn its elemental form, ruthenium has a silvery white metallic appearance. Ruthenium is a rare transition metal belonging to the platinum group of metals. It is found in pentlandite, pyroxenite, and platinum group metal ores. The name Ruthenium originates from the Latin word "Ruthenia," meaning Russia.