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Review
. 2014 Jan;34(1):471-6.

Understanding and improving platinum anticancer drugs--phenanthriplatin

Timothy C Johnstone  1 , Ga Young Park, Stephen J Lippard
Affiliations
Review

Understanding and improving platinum anticancer drugs--phenanthriplatin

Timothy C Johnstone et al. Anticancer Res. 2014 Jan.

Abstract

Approximately half of all patients who receive anticancer chemotherapy are treated with a platinum drug. Despite the widespread use of these drugs, the only cure that can be claimed is that of testicular cancer following cisplatin treatment. This article reviews some of our recent work on phenanthriplatin, a cisplatin derivative in which a chloride ion is replaced by phenanthridine, and on one of its analogues, the previously reported pyriplatin. These cationic complexes form monofunctional adducts on DNA that do not significantly distort the duplex, yet efficiently block transcription. Cell-based assays reveal altered cellular uptake properties and a cancer cell-killing profile different from those of established platinum drugs. Mechanistic work, including a crystal structure analysis of platinum-modified DNA in the active site of RNA polymerase II, is discussed herein.

Keywords: Cytotoxicity; RNA polymerase II; X-ray structure; monofunctional platinum; pyriplatin; review; transcription.

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Conflict of interest statement

Conflicts of Interest

S. J. L. declares a financial interest in Blend Therapeutics.

Figures

Figure 1
Figure 1
Platinum anticancer agents discussed in this review.
See this image and copyright information in PMC

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