KP1019, a new redox-active anticancer agent--preclinical development and results of a clinical phase I study in tumor patients

Chem Biodivers. 2008 Oct;5(10):2140-2155. doi: 10.1002/cbdv.200890195.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents* / adverse effects
  • Antineoplastic Agents* / pharmacokinetics
  • Antineoplastic Agents* / therapeutic use
  • Apoptosis / drug effects
  • Blood Proteins / metabolism
  • Cell Line, Tumor
  • Clinical Trials, Phase I as Topic
  • Drug Screening Assays, Antitumor
  • Drug Stability
  • Humans
  • Indazoles* / adverse effects
  • Indazoles* / pharmacokinetics
  • Indazoles* / therapeutic use
  • Organometallic Compounds
  • Oxidation-Reduction
  • Protein Binding
  • Ruthenium Compounds* / adverse effects
  • Ruthenium Compounds* / pharmacokinetics
  • Ruthenium Compounds* / therapeutic use
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Blood Proteins
  • Indazoles
  • Organometallic Compounds
  • Ruthenium Compounds
  • indazolium trans-(tetrachlorobis(1H-indazole)ruthenate (III))