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

Molecules. 2021 Jul 7;26(14):4132. doi: 10.3390/molecules26144132.

Authors

Adam J Buric¹, Jonathan Dickerhoff¹, Danzhou Yang^{1

2

3

4}

Affiliations

¹ College of Pharmacy, Medicinal Chemistry and Molecular Pharmacology, 575 W Stadium Ave, Purdue University, West Lafayette, IN 47907, USA.
² Center for Cancer Research, Purdue University, 201 S University St, West Lafayette, IN 47906, USA.
³ Department of Chemistry, Purdue University, West Lafayette, IN 47906, USA.
⁴ Purdue Institute for Drug Discovery, West Lafayette, IN 47906, USA.

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 accomplishment 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.

Keywords: DNA; MLN944; NMR; XR5944; anticancer drug; bis-intercalator; major groove binder.

Publication types

Review

MeSH terms

Animals
Antineoplastic Agents / pharmacology*
DNA / chemistry*
Humans
Intercalating Agents / pharmacology*
Neoplasms / drug therapy*
Phenazines / pharmacology*

Substances

Antineoplastic Agents
Intercalating Agents
Phenazines
XR5944
DNA

Abstract

Publication types

MeSH terms

Substances

Grants and funding