Polo-like kinase 1 as target for cancer therapy

Publication type:
Journal article
Metadata:
Autoren
DOI
10.1186/2162-3619-1-38
eISSN
2162-3619
Ausgabe der Veröffentlichung
1
Zeitschrift
Experimental Hematology & Oncology
Sprache
en
Artikelnummer
38
Online publication date
2012
Datum der Veröffentlichung
2012
Status
Published
Herausgeber
Springer Science and Business Media LLC
Herausgeber URL
http://dx.doi.org/10.1186/2162-3619-1-38
Datum der Datenerfassung
2019
Titel
Polo-like kinase 1 as target for cancer therapy
Ausgabe der Zeitschrift
1

Data source: Crossref

Other metadata sources:
Abstract
Polo-like kinase 1 (Plk1) is an interesting molecule both as a biomarker and as a target for highly specific cancer therapy for several reasons. Firstly, it is over-expressed in many cancers and can serve as a biomarker to monitor treatment efficacy of Plk1 inhibitors. Furthermore, the Plk1 enzyme is expressed only in dividing cells and is a major regulator of the cell cycle. It controls entry into mitosis and regulates the spindle checkpoint. The expression of Plk1 in normal cells is not nearly as strong as that in cancer cells, which makes Plk1 a discriminating tartget for the development of cancer-specific small molecule drugs. RNA interference experiments in vitro and in vivo have indicated that downregulation of Plk1 expression represents an attractive concept for cancer therapy. Over the years, a number of Plk1 inhibitors have been discovered. Many of these inhibitors are substances that compete with ATP for the substrate binding site. The ATP-competitive inhibitor BI 6727 is currently being clinically tested in cancer patients. Another drug in development, poloxin, is the first Polo-box domain inhibitor of Plk1. This compound is a derivative of the natural product, thymoquinone, derived from Nigella sativa. A novel and promising strategy is to synthesize bifunctional inhibitors that combine the high binding affinity of ATP inhibitors with the specificity of competitive inhibitors.
Addresses
  • Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128, Mainz, Germany. efferth@uni-mainz.de.
Autoren
DOI
10.1186/2162-3619-1-38
eISSN
2162-3619
Externe Identifier
  • PubMed Identifier: 23227884
  • PubMed Central ID: PMC3533518
Open access
true
ISSN
2162-3619
Ausgabe der Veröffentlichung
1
Zeitschrift
Experimental hematology & oncology
Sprache
eng
Medium
Electronic
Online publication date
2012
Open access status
Open Access
Paginierung
38
Datum der Veröffentlichung
2012
Status
Published
Publisher licence
CC BY
Datum der Datenerfassung
2012
Titel
Polo-like kinase 1 as target for cancer therapy.
Sub types
  • review-article
  • Journal Article
Ausgabe der Zeitschrift
1

Files

https://ehoonline.biomedcentral.com/counter/pdf/10.1186/2162-3619-1-38 https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23227884/pdf/?tool=EBI https://europepmc.org/articles/PMC3533518?pdf=render

Data source: Europe PubMed Central

Abstract
Polo-like kinase 1 (Plk1) is an interesting molecule both as a biomarker and as a target for highly specific cancer therapy for several reasons. Firstly, it is over-expressed in many cancers and can serve as a biomarker to monitor treatment efficacy of Plk1 inhibitors. Furthermore, the Plk1 enzyme is expressed only in dividing cells and is a major regulator of the cell cycle. It controls entry into mitosis and regulates the spindle checkpoint. The expression of Plk1 in normal cells is not nearly as strong as that in cancer cells, which makes Plk1 a discriminating tartget for the development of cancer-specific small molecule drugs. RNA interference experiments in vitro and in vivo have indicated that downregulation of Plk1 expression represents an attractive concept for cancer therapy. Over the years, a number of Plk1 inhibitors have been discovered. Many of these inhibitors are substances that compete with ATP for the substrate binding site. The ATP-competitive inhibitor BI 6727 is currently being clinically tested in cancer patients. Another drug in development, poloxin, is the first Polo-box domain inhibitor of Plk1. This compound is a derivative of the natural product, thymoquinone, derived from Nigella sativa. A novel and promising strategy is to synthesize bifunctional inhibitors that combine the high binding affinity of ATP inhibitors with the specificity of competitive inhibitors.
Date of acceptance
2012
Autoren
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/23227884
DOI
10.1186/2162-3619-1-38
Externe Identifier
  • PubMed Central ID: PMC3533518
ISSN
2162-3619
Ausgabe der Veröffentlichung
1
Zeitschrift
Exp Hematol Oncol
Sprache
eng
Country
England
Paginierung
38
PII
2162-3619-1-38
Datum der Veröffentlichung
2012
Status
Published online
Datum, an dem der Datensatz öffentlich gemacht wurde
2013
Titel
Polo-like kinase 1 as target for cancer therapy.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
1

Data source: PubMed

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