Biochemical and Biophysical Research Communications
Regular ArticleCytotoxic Mechanism of XK469: Resistance of Topoisomerase IIβ Knockout Cells and Inhibition of Topoisomerase I
References (19)
- et al.
Characterization of an amsacrine-resistant line of human leukemia cells. Evidence for a drug-resistant form of topoisomerase II
J. Biol. Chem.
(1989) Selective extraction of polyoma DNA from infected mouse cell cultures
J. Mol. Biol.
(1967)- et al.
Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill
J. Immunol. Methods
(1989) - et al.
Molecular analysis of yeast and human type II topoisomerases—Enzyme-DNA and drug interactions
J. Biol. Chem.
(1999) DNA topoisomerase poisons as antitumor drugs
Annu. Rev. Biochem.
(1989)Topoisomerase inhibitors can selectively interfere with different stages of simian virus 40 DNA replication
Mol. Cell. Biol.
(1986)- et al.
Eukaryotic DNA topoisomerase IIβ
BioEssays
(1998) - et al.
Murine transgenic cells lacking DNA topoisomerase IIβ are resistant to acridines and mitoxantrone: Analysis of cytotoxicity and cleavable complex formation
Mol. Pharmacol.
(1999) - et al.
XK469, a selective topoisomerase IIβ poison
Proc. Natl. Acad. Sci. USA
(1999)
Cited by (21)
Nitric oxide inhibits ATPase activity and induces resistance to topoisomerase II-poisons in human MCF-7 breast tumor cells
2017, Biochemistry and Biophysics ReportsR(+)XK469 inhibits hydroxylation of S-warfarin by CYP2C9
2009, European Journal of CancerCitation Excerpt :XK469 exists as two stereoisomers.2 R(+)XK469 is more potent than S(+)XK469 and has been selected for further clinical trials.9 At least five R(+)XK469 metabolites have been identified.10
Topoisomerase IIα inhibition following DNA transfection greatly enhances random integration in a human pre-B lymphocyte cell line
2009, Biochemical and Biophysical Research CommunicationsCitation Excerpt :A similar isoform-specific inhibitory effect has also been observed with an iron chelator, di-2-pyridylketone-4,4,-dimethyl-3-thiosemicarbazone (Dp44mT) [34]. On the other hand, Snapka et al. reported that XK469, a synthetic quinoxaline phenoxypropionic acid derivative (NSC 697887), acts as a topoisomerase IIβ-selective poison [35], though we showed that the cells with decreased topoisomerase IIα levels exhibited an increased resistance to XK469, similar to topoisomerase IIβ-deficient cells [33]. We have recently demonstrated that NHEJ plays a crucial role in the repair of topoisomerase II inhibitor-induced DNA damage [36–39].
A phase I and pharmacokinetic study of the quinoxaline antitumour Agent R(+)XK469 in patients with advanced solid tumours
2008, European Journal of CancerCitation Excerpt :COMPARE analysis of cytotoxicity data from the NCI-60 cell line screen showed that its mechanism of action is unique in that it was not similar to that of any known cytotoxic agent in the NCI database. Whilst not definitive, the available data suggest that XK469 acts as a selective topoisomerase IIβ inhibitor.5–9 Other proposed mechanisms include XK469-induced inhibition of cyclin B1 ubiquitination10 and apoptosis via binding of the peripheral benzodiazepine receptor.11
TDAE strategy applied to drug-candidate synthesis
2008, Annales Pharmaceutiques Francaises
- 1
To whom correspondence should be addressed. Fax: 614-292-7237. E-mail: [email protected].