KP1019, A New Redox‐Active Anticancer Agent – Preclinical Development and Results of a Clinical Phase I Study in Tumor Patients
Christian G. Hartinger(University of Vienna), Michael A. Jakupec(University of Vienna), Stefanie Zorbas‐Seifried(University of Vienna), Michael Groessl(University of Vienna), Alexander Egger(University of Vienna), Walter Berger(Medical University of Vienna), Haralabos Zorbas(Max Planck Institute of Biochemistry), Paul J. Dyson(École Polytechnique Fédérale de Lausanne), Bernhard K. Keppler(University of Vienna)
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Abstract
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.
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