ArticleBiochemical pharmacology2012
GW583340 and GW2974, human EGFR and HER-2 inhibitors, reverse ABCG2- and ABCB1-mediated drug resistance.
Article in Biochemical pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 61 citations in OpenAlex.
- Anti-HER2-targeted therapies: effects on humanFrontiers in drug delivery · 2025Article
- High-throughput drug screening to investigate blood-brain barrier permeabilityFrontiers in drug delivery · 2024Article
- A Scoping Review on Tyrosine Kinase Inhibitors in Cats: Current Evidence and Future Directions.Animals : an open access journal from MDPI · 2023Article
- Drug resistance of hepatoma cells induced by ATP‑binding cassette transporter G2 by reducing intracellular drug concentration.Experimental and therapeutic medicine · 2023Article
- P-glycoprotein Mediates Resistance to the Anaplastic Lymphoma Kinase Inhiitor Ensartinib in Cancer Cells.Cancers · 2022Article
- The multi-targeted tyrosine kinase inhibitor SKLB610 resensitizes ABCG2-overexpressing multidrug-resistant cancer cells to chemotherapeutic drugs.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Article
- GW-2974 and SCH-442416 modulators of tyrosine kinase and adenosine receptors can also stabilize human telomeric G-quadruplex DNA.PloS one · 2022Article
- How Physiologic Targets Can Be Distinguished from Drug-Binding Proteins.Molecular pharmacology · 2021Article
- Polo-Like Kinase 4's Critical Role in Cancer Development and Strategies for Plk4-Targeted Therapy.Frontiers in oncology · 2021Review
- Overexpression of ABCB1 and ABCG2 contributes to reduced efficacy of the PI3K/mTOR inhibitor samotolisib (LY3023414) in cancer cell lines.Biochemical pharmacology · 2020Article
- BMS-599626, a Highly Selective Pan-HER Kinase Inhibitor, Antagonizes ABCG2-Mediated Drug Resistance.Cancers · 2020Article
- Sitravatinib Sensitizes ABCB1- and ABCG2-Overexpressing Multidrug-Resistant Cancer Cells to Chemotherapeutic Drugs.Cancers · 2020Article
- Cyclooxygenase-2 mediates gefitinib resistance in non-small cell lung cancer through the EGFR/PI3K/AKT axis.Journal of Cancer · 2020Article
- Inhibitor of Interleukin-1 Receptor-associated Kinases 1/4, Can Increase the Sensitivity of Breast Cancer Cells to Methotrexate.International journal of molecular and cellular medicine · 2019Article
- SIS3, a specific inhibitor of Smad3 reverses ABCB1- and ABCG2-mediated multidrug resistance in cancer cell lines.Cancer letters · 2018Article
- Tyrosine kinase inhibitors enhanced the efficacy of conventional chemotherapeutic agent in multidrug resistant cancer cells.Molecular cancer · 2018Review
- Tyrphostin RG14620 selectively reverses ABCG2-mediated multidrug resistance in cancer cell lines.Cancer letters · 2017Article
- Quizartinib (AC220) reverses ABCG2-mediated multidrug resistance:Oncotarget · 2017Article
- Implications of ABCG2 Expression on Irinotecan Treatment of Colorectal Cancer Patients: A Review.International journal of molecular sciences · 2017Review
- Overexpression of ATP-Binding Cassette Subfamily G Member 2 Confers Resistance to Phosphatidylinositol 3-Kinase Inhibitor PF-4989216 in Cancer Cells.Molecular pharmaceutics · 2017Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The overexpression of ATP binding cassette (ABC) transporters often leads to the development of multidrug resistance (MDR) and results in a suboptimal response to chemotherapy. Previously, we reported that lapatinib (GW572016), a human epidermal growth factor receptor (EGFR) and HER-2 tyrosine kinase inhibitor (TKI), significantly reverses MDR in cancer cells by blocking the efflux function of ABC subfamily B member 1 (ABCB1) and ABC subfamily G member 2 (ABCG2). In the present study, we conducted in vitro experiments to evaluate if GW583340 and GW2974, structural analogues of lapatinib, could reverse ABCB1- and ABCG2-mediated MDR. Our results showed that GW583340 and GW2974 significantly sensitized ABCB1 and ABCG2 overexpressing MDR cells to their anticancer substrates. GW583340 and GW2974 significantly increased the intracellular accumulation of [(3)H]-paclitaxel in ABCB1 overexpressing cells and [(3)H]-mitoxantrone in ABCG2 overexpressing cells respectively. In addition, GW583340 and GW2974 significantly inhibited ABCG2-mediated transport of methotrexate in ABCG2 overexpressing membrane vesicles. There was no significant change in the expression levels of ABCB1 and ABCG2 in the cell lines exposed to 5μM of either GW583340 or GW2974 for 3 days. In addition, a docking model predicted the binding conformation of GW583340 and GW2974 to be within the transmembrane region of homology modeled human ABCB1 and ABCG2. We conclude that GW583340 and GW2974, at clinically achievable plasma concentrations, reverse ABCB1- and ABCG2-mediated MDR by blocking the drug efflux function of these transporters. These findings may be useful in developing combination therapy for cancer treatment with EGFR TKIs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.