KP1019, a new redox-active anticancer agent--preclinical development and results of a clinical phase I study in tumor patients.
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 et 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.
Hartinger
Christian G
CG
University of Vienna, Institute of Inorganic Chemistry, Waehringer Strasse 42, A-1090 Vienna, (phone: +43-1-4277-52600; fax: +43-1-4277-52680).|Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne.
Jakupec
Michael A
MA
University of Vienna, Institute of Inorganic Chemistry, Waehringer Strasse 42, A-1090 Vienna, (phone: +43-1-4277-52600; fax: +43-1-4277-52680).
Zorbas-Seifried
Stefanie
S
University of Vienna, Institute of Inorganic Chemistry, Waehringer Strasse 42, A-1090 Vienna, (phone: +43-1-4277-52600; fax: +43-1-4277-52680).|Max Planck Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried.
Groessl
Michael
M
University of Vienna, Institute of Inorganic Chemistry, Waehringer Strasse 42, A-1090 Vienna, (phone: +43-1-4277-52600; fax: +43-1-4277-52680).
Egger
Alexander
A
University of Vienna, Institute of Inorganic Chemistry, Waehringer Strasse 42, A-1090 Vienna, (phone: +43-1-4277-52600; fax: +43-1-4277-52680).
Berger
Walter
W
Institute of Cancer Research, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna.
Zorbas
Haralabos
H
Max Planck Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried.
Dyson
Paul J
PJ
Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne.
Keppler
Bernhard K
BK
University of Vienna, Institute of Inorganic Chemistry, Waehringer Strasse 42, A-1090 Vienna, (phone: +43-1-4277-52600; fax: +43-1-4277-52680).
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001798:Blood Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D017321:Clinical Trials, Phase I as Topic; D004354:Drug Screening Assays, Antitumor; D004355:Drug Stability; D006801:Humans; D007191:Indazoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D009942:Organometallic Compounds; D010084:Oxidation-Reduction; D011485:Protein Binding; D017975:Ruthenium Compounds / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001798:Blood Proteins; D007191:Indazoles; D009942:Organometallic Compounds; D017975:Ruthenium Compounds; C499292:indazolium trans-(tetrachlorobis(1H-indazole)ruthenate (III))