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J Med Chem. 2017 Jun 8;60(11):4517-4532. doi: 10.1021/acs.jmedchem.6b01351. Epub 2017 Feb 28.

A Drug of Such Damned Nature.1 Challenges and Opportunities in Translational Platinum Drug Research.

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1
NCATS Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health , 9800 Medical Center Drive, Rockville, Maryland 20850, United States.

Abstract

The platinum-based anticancer agents cisplatin, carboplatin, and oxaliplatin represent a spectacular translational science achievement. The basic research observations that led to the discovery of Pt complexes as DNA-binding agents that elicit cell arrest, the preclinical tumor regression studies, and the inorganic medicinal chemistry that led to clinical implementation of effective platinum complexes in the clinic have fueled multidisciplinary research into platinum-based drugs. While the successes are clear and the research activity continues, a significant window of time has passed since a new Pt drug has been approved for clinical use. Here we assess the current Pt drug landscape and challenges for future Pt development and discuss opportunities for improving our understanding of Pt drugs that utilize contemporary translational science tools such as chemical biology and real-time imaging. The underexplored spaces may reveal new opportunities for Pt drug development.

PMID:
28195724
DOI:
10.1021/acs.jmedchem.6b01351
[Indexed for MEDLINE]

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