DNA recognition by a novel Bis-Intercalator, potent anticancer drug XR5944

Clement Lin; Danzhou Yang

doi:10.2174/1568026615666150413155608

DNA recognition by a novel Bis-Intercalator, potent anticancer drug XR5944

Clement Lin, Danzhou Yang

Pharmacology and Toxicology

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

XR5944 is a potent anticancer drug with a novel DNA binding mode: DNA bisintercalationg with major groove binding. XR5944 can bind the estrogen response element (ERE) sequence to block ER-ERE binding and inhibit ERα activities, which may be useful for overcoming drug resistance to currently available antiestrogen treatments. This review discusses the progress relating to the structure and function studies of specific DNA recognition of XR5944. The sites of intercalation within a native promoter sequence appear to be different from the ideal binding site and are context- and sequence- dependent. The structural information may provide insights for rational design of improved EREspecific XR5944 derivatives, as well as of DNA bis-intercalators in general.

Original language	English (US)
Pages (from-to)	1385-1397
Number of pages	13
Journal	Current topics in medicinal chemistry
Volume	15
Issue number	12
DOIs	https://doi.org/10.2174/1568026615666150413155608
State	Published - Mar 1 2015

Keywords

Anticancer drug
DNA bis-intercalation
DNA bis-intercalation with major groove binding
NMR solution structure
XR5944 or MLN944

ASJC Scopus subject areas

Drug Discovery

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10.2174/1568026615666150413155608

Cite this

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abstract = "XR5944 is a potent anticancer drug with a novel DNA binding mode: DNA bisintercalationg with major groove binding. XR5944 can bind the estrogen response element (ERE) sequence to block ER-ERE binding and inhibit ERα activities, which may be useful for overcoming drug resistance to currently available antiestrogen treatments. This review discusses the progress relating to the structure and function studies of specific DNA recognition of XR5944. The sites of intercalation within a native promoter sequence appear to be different from the ideal binding site and are context- and sequence- dependent. The structural information may provide insights for rational design of improved EREspecific XR5944 derivatives, as well as of DNA bis-intercalators in general.",

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KW - NMR solution structure

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DNA recognition by a novel Bis-Intercalator, potent anticancer drug XR5944

Abstract

Keywords

ASJC Scopus subject areas

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