Novel DNA Bis-Intercalator XR5944 as a Potent Anticancer Drug-Design and Mechanism of Action.


Journal

Molecules (Basel, Switzerland)
ISSN: 1420-3049
Titre abrégé: Molecules
Pays: Switzerland
ID NLM: 100964009

Informations de publication

Date de publication:
07 Jul 2021
Historique:
received: 28 04 2021
revised: 18 06 2021
accepted: 29 06 2021
entrez: 24 7 2021
pubmed: 25 7 2021
medline: 11 9 2021
Statut: epublish

Résumé

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.

Identifiants

pubmed: 34299405
pii: molecules26144132
doi: 10.3390/molecules26144132
pmc: PMC8304338
pii:
doi:

Substances chimiques

Antineoplastic Agents 0
Intercalating Agents 0
Phenazines 0
XR5944 0
DNA 9007-49-2

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NIGMS NIH HHS
ID : T32 GM125620
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA240346
Pays : United States
Organisme : Foundation for the National Institutes of Health
ID : R01CA177585
Organisme : Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)-Projektnummer
ID : 427347592
Organisme : NCI NIH HHS
ID : R01 CA177585
Pays : United States
Organisme : Foundation for the National Institutes of Health
ID : P30CA023168
Organisme : Foundation for the National Institutes of Health
ID : U01CA240346
Organisme : NCI NIH HHS
ID : P30 CA023168
Pays : United States

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Auteurs

Adam J Buric (AJ)

College of Pharmacy, Medicinal Chemistry and Molecular Pharmacology, 575 W Stadium Ave, Purdue University, West Lafayette, IN 47907, USA.

Jonathan Dickerhoff (J)

College of Pharmacy, Medicinal Chemistry and Molecular Pharmacology, 575 W Stadium Ave, Purdue University, West Lafayette, IN 47907, USA.

Danzhou Yang (D)

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

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Classifications MeSH