ArticleJournal of translational internal medicine2024
RN486, a Bruton's Tyrosine Kinase inhibitor, antagonizes multidrug resistance in ABCG2-overexpressing cancer cells.
Article in Journal of translational internal medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Review
- ABCB6 promotes multidrug resistance in leukemia by mediating drug efflux.Blood science (Baltimore, Md.) · 2026Article
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- Polymethoxylated N-Carboranyl Isoquinolinones: A New Scaffold for ABCG2 Inhibitors.ChemMedChem · 2026Article
- Oridonin targets PRDX1 to promote apoptosis by inducing ROS-mediated ER stress and modulating autophagy.International journal of biological sciences · 2026Article
- SNX9 Orchestrates Lung Metastasis via EGFR-ERK Signaling and Actin Cytoskeleton Remodeling in Breast Cancer.Oncology research · 2026Article
- Antibody-drug conjugates in colorectal cancer: advances in targeted delivery and personalized oncology.Frontiers in bioengineering and biotechnology · 2026Review
- Reversal of ABCG2-mediated MDR by VEGFR3 inhibitor (S)-SAR131675.Frontiers in pharmacology · 2026Article
- A Serum-Stable Antimicrobial Peptide-Based Delivery Platform for Selective Treatment of Nontargetable and Chemoresistant Tumors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Clinical approaches to overcome PARP inhibitor resistance.Molecular cancer · 2025Review
- Decoding tumor angiogenesis: pathways, mechanisms, and future directions in anti-cancer strategies.Biomarker research · 2025Review
- Fluorinated small molecule derivatives in cancer immunotherapy: emerging frontiers and therapeutic potential.Frontiers in immunology · 2025Review
- Synergistic anticancer and antibacterial effects of novel regimens of phytopolyphenols and repurposing drugs on cultured cells.Oncology research · 2025Article
- Advancements in Protein Kinase Inhibitors: From Discovery to Clinical Applications.Research (Washington, D.C.) · 2025Review
- Reversal of ABCG2-mediated drug resistance by tinodasertib (ETC-206).Frontiers in pharmacology · 2025Article
- c-MET tyrosine kinase inhibitors reverse drug resistance mediated by the ATP-binding cassette transporter B1 (ABCB1) in cancer cells.3 Biotech · 2025Article
- Molecular docking and MD simulation approach to identify potential phytochemical lead molecule against triple negative breast cancer.F1000Research · 2024Article
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10 authors.
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Abstract
Background and Objectives: Overcoming ATP-binding cassette subfamily G member 2 (ABCG2)-mediated multidrug resistance (MDR) has attracted the attention of scientists because one of the critical factors resulting in MDR in cancer is the overexpression of ABCG2. RN486, a Bruton's Tyrosine Kinase (BTK) inhibitor, was discovered to potentially reverse ABCB1-mediated MDR. However, there is still uncertainty about whether RN486 has a reversal off-target impact on ABCG2-mediated MDR. Methods: MTT assay was used to detect the reversal effect of RN486 on ABCG2-overexpressing cancer cells. The ABCG2 expression level and subcellular localization were examined by Western blotting and immunofluorescence. Drug accumulation and eflux assay and ATPase assay were performed to analyze the ABCG2 transporter function and ATPase activity. Molecular modeling predicted the binding between RN486 and ABCG2 protein. Results: Non-toxic concentrations of RN486 remarkably increased the sensitivity of ABCG2-overexpressing cancer cells to conventional anticancer drugs mitoxantrone and topotecan. The reversal mechanistic studies showed that RN486 elevated the drug accumulation because of reducing the eflux of ABCG2 substrate drug in ABCG2-overexpressing cancer cells. In addition, the inhibitory efect of RN486 on ABCG2-associated ATPase activity was also verified. Molecular docking study implied a strong binding afinity between RN486 and ABCG2 transporter. Meanwhile, the ABCG2 subcellular localization was not altered by the treatment of RN486, but the expression level of ABCG2 was down-regulated. Conclusions: Our studies propose that RN486 can antagonize ABCG2-mediated MDR in cancer cells via down-regulating the expression level of ABCG2 protein, reducing ATPase activity of ABCG2 transporter, and inhibiting the transporting function. RN486 could be potentially used in conjunction with chemotherapy to alleviate MDR mediated by ABCG2 in cancer.
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