Identification of new P-glycoprotein inhibitors derived from cardiotonic steroids
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Maen Zeino
- Malte S Paulsen
- Martin Zehl
- Ernst Urban
- Brigitte Kopp
- Thomas Efferth
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000348264400002&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1016/j.bcp.2014.10.009
- eISSN
- 1873-2968
- Externe Identifier
- Clarivate Analytics Document Solution ID: AZ5MG
- PubMed Identifier: 25451686
- ISSN
- 0006-2952
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- BIOCHEMICAL PHARMACOLOGY
- Schlüsselwörter
- Cardiotonic steroids
- Chemotherapy
- Multidrug resistance reversal
- P-glycoprotein
- Paginierung
- 11 - 24
- Datum der Veröffentlichung
- 2015
- Status
- Published
- Titel
- Identification of new P-glycoprotein inhibitors derived from cardiotonic steroids
- Sub types
- Article
- Ausgabe der Zeitschrift
- 93
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Autoren
- Maen Zeino
- Malte S Paulsen
- Martin Zehl
- Ernst Urban
- Brigitte Kopp
- Thomas Efferth
- DOI
- 10.1016/j.bcp.2014.10.009
- ISSN
- 0006-2952
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- Biochemical Pharmacology
- Sprache
- en
- Paginierung
- 11 - 24
- Datum der Veröffentlichung
- 2015
- Status
- Published
- Herausgeber
- Elsevier BV
- Herausgeber URL
- http://dx.doi.org/10.1016/j.bcp.2014.10.009
- Datum der Datenerfassung
- 2018
- Titel
- Identification of new P-glycoprotein inhibitors derived from cardiotonic steroids
- Ausgabe der Zeitschrift
- 93
Data source: Crossref
- Abstract
- P-glycoprotein (ABCB1, MDR1) is capable of extruding chemotherapeutics outside the cell and its overexpression in certain cancer cells may cause failure of chemotherapy. Many attempts were carried out to identify potent inhibitors of this transporter and numerous compounds were shown to exert inhibitory effects in vitro, but so far none were able to make their way to the clinic due to serious complications. Natural compounds represent a great source of therapeutics, which are believed to be safe and effective. Therefore, we have screened a large library of naturally occurring cardiotonic steroids and their derivatives using high throughput flow cytometry. We were able to identify six compounds capable of modulating P-glycoprotein activity. By using P-glycoprotein ATPase assays, molecular docking in silico studies and resazurin reduction assays, the outcome of this high throughput screening platform has been validated. These novel compounds may serve as candidates to reverse doxorubicin resistance in leukemia cells.
- Addresses
- Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.
- Autoren
- Maen Zeino
- Malte S Paulsen
- Martin Zehl
- Ernst Urban
- Brigitte Kopp
- Thomas Efferth
- Thomas Efferth
- DOI
- 10.1016/j.bcp.2014.10.009
- eISSN
- 1873-2968
- Externe Identifier
- PubMed Identifier: 25451686
- Open access
- false
- ISSN
- 0006-2952
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- Biochemical pharmacology
- Schlüsselwörter
- Cell Line
- Humans
- Doxorubicin
- Cardiac Glycosides
- Cell Survival
- Protein Structure, Secondary
- Protein Structure, Tertiary
- Dose-Response Relationship, Drug
- ATP Binding Cassette Transporter, Subfamily B, Member 1
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2014
- Paginierung
- 11 - 24
- Datum der Veröffentlichung
- 2015
- Status
- Published
- Datum der Datenerfassung
- 2014
- Titel
- Identification of new P-glycoprotein inhibitors derived from cardiotonic steroids.
- Sub types
- Research Support, Non-U.S. Gov't
- Journal Article
- Ausgabe der Zeitschrift
- 93
Data source: Europe PubMed Central
- Abstract
- P-glycoprotein (ABCB1, MDR1) is capable of extruding chemotherapeutics outside the cell and its overexpression in certain cancer cells may cause failure of chemotherapy. Many attempts were carried out to identify potent inhibitors of this transporter and numerous compounds were shown to exert inhibitory effects in vitro, but so far none were able to make their way to the clinic due to serious complications. Natural compounds represent a great source of therapeutics, which are believed to be safe and effective. Therefore, we have screened a large library of naturally occurring cardiotonic steroids and their derivatives using high throughput flow cytometry. We were able to identify six compounds capable of modulating P-glycoprotein activity. By using P-glycoprotein ATPase assays, molecular docking in silico studies and resazurin reduction assays, the outcome of this high throughput screening platform has been validated. These novel compounds may serve as candidates to reverse doxorubicin resistance in leukemia cells.
- Date of acceptance
- 2014
- Autoren
- Maen Zeino
- Malte S Paulsen
- Martin Zehl
- Ernst Urban
- Brigitte Kopp
- Thomas Efferth
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/25451686
- DOI
- 10.1016/j.bcp.2014.10.009
- eISSN
- 1873-2968
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- Biochem Pharmacol
- Schlüsselwörter
- Cardiotonic steroids
- Chemotherapy
- Multidrug resistance reversal
- P-glycoprotein
- ATP Binding Cassette Transporter, Subfamily B, Member 1
- Cardiac Glycosides
- Cell Line
- Cell Survival
- Dose-Response Relationship, Drug
- Doxorubicin
- Humans
- Protein Structure, Secondary
- Protein Structure, Tertiary
- Sprache
- eng
- Country
- England
- Paginierung
- 11 - 24
- PII
- S0006-2952(14)00627-3
- Datum der Veröffentlichung
- 2015
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2015
- Titel
- Identification of new P-glycoprotein inhibitors derived from cardiotonic steroids.
- Sub types
- Journal Article
- Research Support, Non-U.S. Gov't
- Ausgabe der Zeitschrift
- 93
Data source: PubMed
- Beziehungen:
- Property of