KP1019, A New Redox-Active Anticancer Agent - Preclinical Development and Results of a Clinical Phase I Study in Tumor Patients

被引：767

作者：

Hartinger, Christian G. ^{[1
,2
]}

Jakupec, Michael A. ^{[1
]}

Zorbas-Seifried, Stefanie ^{[1
,3
]}

Groessl, Michael ^{[1
]}

Egger, Alexander ^{[1
]}

Berger, Walter ^{[4
]}

Zorbas, Haralabos ^{[3
]}

Dyson, Paul J. ^{[2
]}

Keppler, Bernhard K. ^{[1
]}

机构：

[1] Univ Vienna, Inst Inorgan Chem, A-1090 Vienna, Austria

[2] Ecole Polytech Fed Lausanne, Inst Sci & Ingn Chim, CH-1015 Lausanne, Switzerland

[3] Max Planck Inst Biochem, D-82152 Martinsried, Germany

[4] Med Univ Vienna, Inst Canc Res, A-1090 Vienna, Austria

来源：

CHEMISTRY & BIODIVERSITY | 2008年 / 5卷 / 10期

基金：

奥地利科学基金会;

关键词：

D O I：

10.1002/cbdv.200890195

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The promising drug candidate indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019) is the second Ru-based anticancer agent to enter clinical trials. In this review, which is an update of a paper from 2006 (Hartinger al., J. Inorg. Biochem. 2006,100, 891-904), the experimental evidence for the proposed mode of action of this coordination compound is discussed, including transport into the cell via the transferrin cycle and activation by reduction. The results of the early clinical development of KP1019 are summarized in which five out of six evaluated patients experienced disease stabilization with no severe side effects.

引用

页码：2140 / 2155

页数：16

共 98 条

[71] A comparative study of adduct formation between the anticancer ruthenium(III) compound HInd trans-[RuCl4(Ind)2] and serum proteins [J].

Piccioli, F ;

Sabatini, S ;

Messori, L ;

Orioli, P ;

Hartinger, CG ;

Keppler, BK .

JOURNAL OF INORGANIC BIOCHEMISTRY, 2004, 98 (06) :1135-1142

[72]

Pieper T, 1998, ANALUSIS, V26, pM84

[73]

PIEPER T, 1999, TOP BIOL INORG CHEM, V1, P171

[74] Platinum group metallodrug-protein binding studies by capillary electrophoresis - inductively coupled plasma-mass spectrometry: A further insight into the reactivity of a novel antitumor ruthenium(III) complex toward human serum proteins [J].

Polec-Pawlak, K ;

Abramski, JK ;

Semenova, O ;

Hartinger, CG ;

Timerbaev, AR ;

Keppler, BK ;

Jarosz, M .

ELECTROPHORESIS, 2006, 27 (5-6) :1128-1135

[75] Application of capillary electrophoresis-inductively coupled plasma mass spectrometry to comparative studying of the reactivity of antitumor ruthenium(III) complexes differing in the nature of counter-ion toward human serum proteins [J].

Polec-Pawlak, Kasia ;

Abramski, Jan K. ;

Ferenc, Julia ;

Foteeva, Lidia S. ;

Timerbaev, Andrei R. ;

Keppler, Bernhard K. ;

Jarosz, Maciej .

JOURNAL OF CHROMATOGRAPHY A, 2008, 1192 (02) :323-326

[76] The changing faces of glutathione, a cellular protagonist [J].

Pompella, A ;

Visvikis, A ;

Paolicchi, A ;

De Tata, V ;

Casini, AF .

BIOCHEMICAL PHARMACOLOGY, 2003, 66 (08) :1499-1503

[77] Transferrin binding and transferrin-mediated cellular uptake of the ruthenium coordination compound KP1019, studied by means of AAS, ESI-MS and CD spectroscopy [J].

Pongratz, M ;

Schluga, P ;

Jakupec, MA ;

Arion, VB ;

Hartinger, CG ;

Allmaier, G ;

Keppler, BK .

JOURNAL OF ANALYTICAL ATOMIC SPECTROMETRY, 2004, 19 (01) :46-51

[78] Why does cisplatin reach guanine-N7 with competing S-donor ligands available in the cell? [J].

Reedijk, J .

CHEMICAL REVIEWS, 1999, 99 (09) :2499-2510

[79] Tuning of redox potentials for the design of ruthenium anticancer drugs -: An electrochemical study of [trans-RuCl4L(DMSO)]- and [trans-RuCl42]- complexes, where L = imidazole, 1,2,4-triazole, indazole [J].

Reisner, E ;

Arion, VB ;

Fátima, M ;

da Silva, CG ;

Lichtenecker, R ;

Eichinger, A ;

Keppler, BK ;

Kukushkin, VY ;

Pombeiro, AJL .

INORGANIC CHEMISTRY, 2004, 43 (22) :7083-7093

[80]

Reisner E., 2005, ED ADV CHEM, P215

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