Novel dna bis-intercalator xr5944 as a potent anticancer drug—design and mechanism of action

Adam J. Buric; Jonathan Dickerhoff; Danzhou Yang

doi:10.3390/molecules26144132

Novel dna bis-intercalator xr5944 as a potent anticancer drug—design and mechanism of action

Adam J. Buric, Jonathan Dickerhoff, Danzhou Yang

Pharmacology and Toxicology

Research output: Contribution to journal › Review article › peer-review

7 Scopus citations

Abstract

This review is dedicated to Professor William A. Denny’s discovery of XR5944 (also known as MLN944). XR5944 is a DNA-targeted agent with exceptionally potent antitumor activity and a novel DNA binding mode, bis-intercalation and major groove binding, as well as a novel mechanism of action, transcription inhibition. This novel anticancer compound represents a remarkable accom-plishment resulting from two decades of drug discovery by Professor Denny and coworkers. Here, we review our work on the structural study of the DNA binding mode of XR5944 and mechanistic study of XR5944 action.

Original language	English (US)
Article number	4132
Journal	Molecules
Volume	26
Issue number	14
DOIs	https://doi.org/10.3390/molecules26144132
State	Published - Jul 2 2021

Keywords

Anticancer drug
Bis-intercalator
DNA
MLN944
Major groove binder
NMR
XR5944

ASJC Scopus subject areas

Analytical Chemistry
Chemistry (miscellaneous)
Molecular Medicine
Pharmaceutical Science
Drug Discovery
Physical and Theoretical Chemistry
Organic Chemistry

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title = "Novel dna bis-intercalator xr5944 as a potent anticancer drug—design and mechanism of action",

abstract = "This review is dedicated to Professor William A. Denny{\textquoteright}s discovery of XR5944 (also known as MLN944). XR5944 is a DNA-targeted agent with exceptionally potent antitumor activity and a novel DNA binding mode, bis-intercalation and major groove binding, as well as a novel mechanism of action, transcription inhibition. This novel anticancer compound represents a remarkable accom-plishment resulting from two decades of drug discovery by Professor Denny and coworkers. Here, we review our work on the structural study of the DNA binding mode of XR5944 and mechanistic study of XR5944 action.",

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AU - Dickerhoff, Jonathan

AU - Yang, Danzhou

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AB - This review is dedicated to Professor William A. Denny’s discovery of XR5944 (also known as MLN944). XR5944 is a DNA-targeted agent with exceptionally potent antitumor activity and a novel DNA binding mode, bis-intercalation and major groove binding, as well as a novel mechanism of action, transcription inhibition. This novel anticancer compound represents a remarkable accom-plishment resulting from two decades of drug discovery by Professor Denny and coworkers. Here, we review our work on the structural study of the DNA binding mode of XR5944 and mechanistic study of XR5944 action.

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Novel dna bis-intercalator xr5944 as a potent anticancer drug—design and mechanism of action

Abstract

Keywords

ASJC Scopus subject areas

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