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

[1] Characterization of interactions between human serum albumin and tumor-inhibiting amino alcohol platinum(II) complexes using capillary electrophoresis [J].

Aleksenko, Svetlana S. ;

Hartinger, Christian G. ;

Semenova, Olga ;

Meelich, Kristof ;

Timerbaev, Andrei R. ;

Keppler, Bernhard K. .

JOURNAL OF CHROMATOGRAPHY A, 2007, 1155 (02) :218-221

[2] Determination of drug binding sites to proteins by electrospray ionisation mass spectrometry: the interaction of cisplatin with transferrin [J].

Allardyce, CS ;

Dyson, PJ ;

Coffey, J ;

Johnson, N .

RAPID COMMUNICATIONS IN MASS SPECTROMETRY, 2002, 16 (10) :933-935

[3] Inductively coupled plasma mass spectrometry to identify protein drug targets from whole cell systems [J].

Allardyce, CS ;

Dyson, PJ ;

Abou-Shakra, FR ;

Birtwistle, H ;

Coffey, J .

CHEMICAL COMMUNICATIONS, 2001, (24) :2708-2709

[4] Strategy to tether organometallic ruthenium-arene anticancer compounds to recombinant human serum albumin [J].

Ang, Wee Han ;

Daldini, Elisa ;

Juillerat-Jeanneret, Lucienne ;

Dyson, Paul J. .

INORGANIC CHEMISTRY, 2007, 46 (22) :9048-9050

[5] Development of organometallic ruthenium-arene anticancer drugs that resist hydrolysis [J].

Ang, Wee Han ;

Daldini, Elisa ;

Scolaro, Claudine ;

Scopelliti, Rosario ;

Juillerat-Jeannerat, Lucienne ;

Dyson, Paul J. .

INORGANIC CHEMISTRY, 2006, 45 (22) :9006-9013

[6] Classical and non-classical ruthenium-based anticancer drugs: Towards targeted chemotherapy [J].

Ang, Wee Han ;

Dyson, Paul J. .

EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, 2006, (20) :4003-4018

[7]

[Anonymous], 1999, TOP BIOL INORG CHEM

[8] Ascorbic acid: much more than just an antioxidant [J].

Arrigoni, O ;

De Tullio, MC .

BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 2002, 1569 (1-3) :1-9

[9]

BERGER MR, 1989, ANTICANCER RES, V9, P761

[10]

CARTER DC, 1994, ADV PROTEIN CHEM, V45, P153

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