A phase I dose-escalation study of NKP-1339 in patients with advanced solid tumors refractory to treatment.

Dickson, N; Jones, Suzanne F.; Burris, H. A.; Ramanathan, R. K.; Weiss, Glen J.; Infante, J. R.; Bendell, J. C.; McCulloch, William; Hoff, Daniel D. Von

doi:10.1200/jco.2011.29.15_suppl.2607

Cited by 33 publications

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“…indazole)ruthenate(III)] (KP1019) [5] and its sodium salt (NKP1339/IT-139) [6] are under clinical evaluations with promising results. It has been recently reported that the catalytic activity of the [Ru(II)( 6 -p-cymene)] complexes of sulfonamido ethyleneamine ligands can be transferred in cancer cells, which has influence on the extent of intracellular conversion of NAD + to NADH.…”

Section: Compounds Namely Imidazolium Trans-[tetrachlorido(dmso)(imimentioning

confidence: 99%

“…Rh(III) is isoelectronic with Ru(II), and the kinetic intertness of the [Rh(H 2 O) 6 ] 3+ complex can be overcome by coordination of neutral arene or especially by anionic pentamethylcyclopentadienyl ligands [8,9]. Among the half-sandwich organorhodium compounds foremost (η 5 -pentamethylcyclopentadienyl)rhodium(III) (RhCp*) complexes of 1,3,5-triaza-7-phosphatricyclo-[3.3.1.1]decane (PTA) were tested for in vitro antiproliferative activity, but their efficacy was negligible [10].…”

Section: Compounds Namely Imidazolium Trans-[tetrachlorido(dmso)(imimentioning

confidence: 99%

“…However, the RhCp* complexes of the simplest bidentate alkylamino and aromatic N-donor ligands, namely ethylenediamine (en) and 2,2'-bipyridine (bpy) did not show significant cytotoxicity (IC 50 >100 μM measured in MCF-7 and HT-29 cells) [17]. On the contrary the antiproliferative activity of [Ru(II)( 6 -p-cymene)(en)Cl]PF 6 and [Ru(II)( 6 -biphenyl)(en)Cl]PF 6 complexes developed in the laboratory of Sadler is comparable to carboplatin (IC 50 6-9 μM measured in A2780 cells) [18].…”

Section: Compounds Namely Imidazolium Trans-[tetrachlorido(dmso)(imimentioning

confidence: 99%

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Comparative solution equilibrium studies on pentamethylcyclopentadienyl rhodium complexes of 2,2ʹ-bipyridine and ethylenediamine and their interaction with human serum albumin

Enyedy

Mészáros

Dömötör

et al. 2015

Journal of Inorganic Biochemistry

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Complex formation equilibrium processes of the (N,N) donor containing 2,2'-bipyridine (bpy) and ethylenediamine (en) with (η 5 -pentamethylcyclopentadienyl)rhodium(III) were investigated in aqueous solution via pH-potentiometry, 1 H NMR spectroscopy, and UV-Vis spectrophotometry in the absence and presence of chloride ions. 2+ , and formation of ternary HSA-RhCp*-ligand adducts was proved. In the case of the deferiprone complex, the RhCp* fragment is cleaved off when HSA is loaded with low equivalents of the compound.

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Section: Compounds Namely Imidazolium Trans-[tetrachlorido(dmso)(imimentioning

confidence: 99%

Section: Compounds Namely Imidazolium Trans-[tetrachlorido(dmso)(imimentioning

confidence: 99%

Section: Compounds Namely Imidazolium Trans-[tetrachlorido(dmso)(imimentioning

confidence: 99%

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Comparative solution equilibrium studies on pentamethylcyclopentadienyl rhodium complexes of 2,2ʹ-bipyridine and ethylenediamine and their interaction with human serum albumin

Enyedy

Mészáros

Dömötör

et al. 2015

Journal of Inorganic Biochemistry

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“…Numerous metal complexes have been synthesized and tested as potential anticancer or antimetastatic agents. Some of them have entered phase I or II clinical [3] and its sodium salt (NKP-1339/IT-139) with an increased water solubility [4], imidazolium trans-…”

Section: Introductionmentioning

confidence: 99%

“…Electron paramagnetic resonance spin labeling of HSA revealed that indazolium trans-[RuCl 4 (1H-indazole)(NO)] and long-chain fatty acids show competitive binding to HSA.…”

mentioning

confidence: 99%

Investigation of the binding of cis/trans-[MCl4(1H-indazole)(NO)]− (M = Ru, Os) complexes to human serum albumin

Dömötör

Rathgeb

Kuhn

et al. 2016

Journal of Inorganic Biochemistry

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Overall binding affinity of sodium or indazolium cis/trans-[MCl 4 (1H-indazole)(NO)] (M = Ru,Os) complexes towards human serum albumin (HSA) and high molecular mass components of the blood serum was monitored by ultrafiltration. HSA was found to be mainly responsible for the binding of the studied ruthenium and osmium complexes. In other words, this protein can provide a depot for the compounds and can affect their biodistribution and transport processes. In order to elucidate the HSA binding sites tryptophan fluorescence quenching studies and displacement reactions with the established site markers warfarin and dansylglycine were performed. Conditional stability constants for the binding to sites I and II on HSA were computed showing that the studied ruthenium and osmium complexes are able to bind into both sites with moderately strong affinity (logK' = 4.4-5.1). Site I is slightly more favored over site II for all complexes. No significant differences in the HSA binding properties were found for these metal complexes demonstrating negligible influence of the type of counter ion (sodium vs. indazolium), the metal ion center identity (Ru vs. Os) or the position of the nitrosyl group on the binding 2 event. Electron paramagnetic resonance spin labeling of HSA revealed that indazolium trans-[RuCl 4 (1H-indazole)(NO)] and long-chain fatty acids show competitive binding to HSA.Moreover, this complex has a higher affinity for site I, but when present in excess, it is able to bind to site II as well, and displace fatty acids.

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Ruthenium Anticancer Agents—From Cisplatin Analogues to Rational Drug Design

Adams

Hanif

Hartinger

2017

Encyclopedia of Inorganic and Bioinorganic Chemistry

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The discovery of cisplatin has triggered research in metal‐based anticancer agents. Ruthenium complexes have been investigated as chemotherapeutics for more than 30 years. In this article, we review the early steps of Ru‐based drug development, which was often based on the structural similarity to cisplatin, and led eventually to the clinical trials of KP1019/KP1339 and NAMI‐A and the emergence of the organometallic RAPTA and RAED compound series. The unique modes of action of Ru compounds equip them with their special pharmacological properties. Especially in the past decades, many rationally designed Ru complexes have been reported to expand the range of compound types, and therewith the modes of action these compounds follow. This article covers many of the reported novel approaches and newer developments in the field, demonstrating in some cases properties advantageous to that of platinum anticancer agents and opening the route to new generations of metal‐based anticancer agents.

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A phase I dose-escalation study of NKP-1339 in patients with advanced solid tumors refractory to treatment.

Cited by 33 publications

References 0 publications

Comparative solution equilibrium studies on pentamethylcyclopentadienyl rhodium complexes of 2,2ʹ-bipyridine and ethylenediamine and their interaction with human serum albumin

Comparative solution equilibrium studies on pentamethylcyclopentadienyl rhodium complexes of 2,2ʹ-bipyridine and ethylenediamine and their interaction with human serum albumin

Investigation of the binding of cis/trans-[MCl4(1H-indazole)(NO)]− (M = Ru, Os) complexes to human serum albumin

Ruthenium Anticancer Agents—From Cisplatin Analogues to Rational Drug Design

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