Cited by 35Drug Transport and Resistance MechanismsAntibiotic Resistance in BacteriaPharmacogenetics and Drug Metabolism

AST1306, a potent EGFR inhibitor, antagonizes ATP-binding cassette subfamily G member 2-mediated multidrug resistance

Zhang, Hui, Wang, Yi-Jun, Zhang, Yun-Kai, Wang, De-Shen, Kathawala, Rishil J., Patel, Atish, Talele, Tanaji T., Chen, Zhe-Sheng +1 more·2014·Cancer Letters

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.

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Crossref · 10.1016/j.canlet.2014.04.008

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Authors
Zhang, H., Wang, Y.-J., Zhang, Y.-K., Wang, D.-S., Kathawala, R. J., Patel, A., Talele, T. T., Chen, Z.-S., & Fu, L.-W.
Affiliations
St. John's University (US)
Corresponding author
Chen, Zhe-Sheng
Venue
Cancer Letters
Publisher
Elsevier BV
Published
2014-08
Volume
350
Issue
1-2
Pages
61-68
ISSN
0304-3835 (ISSN-L)
OpenAlex
W1983688434
Cited by
34
References
47
Citations by year
2026: 1 · 2024: 1 · 2023: 4 · 2021: 2 · 2020: 1 · 2018: 6 · 2017: 5 · 2016: 3 · 2015: 6 · 2014: 5
FWCI
3.06
Type
journal article
Language
en
Open access
closed
Locations
  • Cancer Letters (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Keywords
EGFR inhibitors, ERBB2, ABCG2, multidrug resistance reversal, ABC transporters, drug efflux, homology modeling
MeSH terms
ATP Binding Cassette Transporter, Subfamily G, Member 2, Acrylamides, Antineoplastic Agents, Biological Transport, Humans, Mitoxantrone, Neoplasm Proteins, Quinazolines, Drug Resistance, Multiple, ATP-Binding Cassette Transporters, Erb-b2 Receptor Tyrosine Kinases, Receptor, ErbB-2, Drug Resistance, Neoplasm, Cell Line, Tumor, Protein Kinase Inhibitors, Molecular Docking Simulation, ErbB Receptors

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