Back to Search
Start Over
AST1306, a potent EGFR inhibitor, antagonizes ATP-binding cassette subfamily G member 2-mediated multidrug resistance.
- Source :
-
Cancer letters [Cancer Lett] 2014 Aug 01; Vol. 350 (1-2), pp. 61-8. Date of Electronic Publication: 2014 Apr 18. - Publication Year :
- 2014
-
Abstract
- AST1306, an inhibitor of EGFR and ErbB2, is currently in phase I of clinical trials. We evaluated the effect of AST306 on the reversal of multidrug resistance (MDR) induced by ATP-binding cassette (ABC) transporters. We found that AST1306 significantly sensitized the ABC subfamily G member 2 (ABCG2)-overexpressing cells to ABCG2 substrate chemotherapeutics. AST1306 significantly increased intracellular accumulation of [(3)H]-mitoxantrone in ABCG2-overexpressing cells by blocking ABCG2 efflux function. Moreover, AST1306 stimulated the ATPase activity of ABCG2. Homology modeling predicted the binding conformation of AST1306 to be within the transmembrane region of ABCG2. In conclusion, AST1306 could notably reverse ABCG2-mediated MDR.<br /> (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
- Subjects :
- ATP Binding Cassette Transporter, Subfamily G, Member 2
Antineoplastic Agents pharmacology
Cell Line, Tumor
ErbB Receptors antagonists & inhibitors
Humans
Mitoxantrone chemistry
Molecular Docking Simulation
Protein Kinase Inhibitors pharmacology
Receptor, ErbB-2 antagonists & inhibitors
ATP-Binding Cassette Transporters antagonists & inhibitors
Acrylamides pharmacology
Biological Transport drug effects
Drug Resistance, Multiple drug effects
Drug Resistance, Neoplasm drug effects
Neoplasm Proteins antagonists & inhibitors
Quinazolines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7980
- Volume :
- 350
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- Cancer letters
- Publication Type :
- Academic Journal
- Accession number :
- 24747122
- Full Text :
- https://doi.org/10.1016/j.canlet.2014.04.008