ArticleMolecular cancer therapeutics2012
The novel BCR-ABL and FLT3 inhibitor ponatinib is a potent inhibitor of the MDR-associated ATP-binding cassette transporter ABCG2.
Article in Molecular cancer therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 89 citations in OpenAlex.
- Trial
- Characterizing P-glycoprotein and Breast Cancer Resistance Protein interactions of asciminib among other tyrosine kinase inhibitors used in chronic myeloid leukemia.Cancer chemotherapy and pharmacology · 2026Article
- ABCG2-autophagy regulatory axis in cancer stem cells: implication in cancer metastasis, recurrence and chemotherapy resistance.Cell communication and signaling : CCS · 2026Review
- Repurposing the Tyrosine Kinase Inhibitors Targeting FGFR and VEGFR Pathways for Cancer Therapy: A Comprehensive Review.Cancers · 2025Review
- c-MET tyrosine kinase inhibitors reverse drug resistance mediated by the ATP-binding cassette transporter B1 (ABCB1) in cancer cells.3 Biotech · 2025Article
- Computationally Driven Discovery of a BCR-ABL1 Kinase Inhibitor with Activity in Multidrug-Resistant Chronic Myeloid Leukemia.Journal of medicinal chemistry · 2024Article
- RN486, a Bruton's Tyrosine Kinase inhibitor, antagonizes multidrug resistance in ABCG2-overexpressing cancer cells.Journal of translational internal medicine · 2024Article
- ATP-Binding Cassette Subfamily G Member 2 in Acute Myeloid Leukemia: A New Molecular Target?Biomedicines · 2024Review
- Multidrug resistance transporters P-gp and BCRP limit the efficacy of ATR inhibitor ceralasertib in cancer cells.Frontiers in pharmacology · 2024Article
- Transporter-Mediated Cellular Distribution of Tyrosine Kinase Inhibitors as a Potential Resistance Mechanism in Chronic Myeloid Leukemia.Pharmaceutics · 2023Review
- The acquisition order of leukemic drug resistance mutations is directed by the selective fitness associated with each resistance mechanism.Scientific reports · 2023Article
- ABCG2 in Acute Myeloid Leukemia: Old and New Perspectives.International journal of molecular sciences · 2023Review
- Allogeneic stem cell transplantation in the treatment of acute myeloid leukemia: An overview of obstacles and opportunities.World journal of clinical cases · 2023Review
- The AKT inhibitor, MK-2206, attenuates ABCG2-mediated drug resistance in lung and colon cancer cells.Frontiers in pharmacology · 2023Article
- Molecular Mechanisms of Tyrosine Kinase Inhibitor Resistance in Chronic Myeloid Leukemia.Handbook of experimental pharmacology · 2023Review
- A curated binary pattern multitarget dataset of focused ATP-binding cassette transporter inhibitors.Scientific data · 2022Article
- Transport and metabolism of tyrosine kinase inhibitors associated with chronic myeloid leukemia therapy: a review.Molecular and cellular biochemistry · 2022Review
- Rotating between ponatinib and imatinib temporarily increases the efficacy of imatinib as shown in a chronic myeloid leukaemia model.Scientific reports · 2022Article
- Infigratinib (BGJ 398), a Pan-FGFR Inhibitor, Targets P-Glycoprotein and Increases Chemotherapeutic-Induced Mortality of Multidrug-Resistant Tumor Cells.Biomedicines · 2022Article
- Hybrids of Imatinib with Quinoline: Synthesis, Antimyeloproliferative Activity Evaluation, and Molecular Docking.Pharmaceuticals (Basel, Switzerland) · 2022Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Ponatinib is a novel tyrosine kinase inhibitor with potent activity against BCR-ABL with mutations, including T315I, and also against fms-like tyrosine kinase 3. We tested interactions between ponatinib at pharmacologically relevant concentrations of 50 to 200 nmol/L and the MDR-associated ATP-binding cassette (ABC) proteins ABCB1, ABCC1, and ABCG2. Ponatinib enhanced uptake of substrates of ABCG2 and ABCB1, but not ABCC1, in cells overexpressing these proteins, with a greater effect on ABCG2 than on ABCB1. Ponatinib potently inhibited [(125)I]-IAAP binding to ABCG2 and ABCB1, indicating binding to their drug substrate sites, with IC(50) values of 0.04 and 0.63 μmol/L, respectively. Ponatinib stimulated ABCG2 ATPase activity in a concentration-dependent manner and stimulated ABCB1 ATPase activity at low concentrations, consistent with it being a substrate of both proteins at pharmacologically relevant concentrations. The ponatinib IC(50) values of BCR-ABL-expressing K562 cells transfected with ABCB1 and ABCG2 were approximately the same as and 2-fold higher than that of K562, respectively, consistent with ponatinib being a substrate of both proteins, but inhibiting its own transport, and resistance was also attenuated to a small degree by ponatinib-induced downregulation of ABCB1 and ABCG2 cell-surface expression on resistant K562 cells. Ponatinib at pharmacologically relevant concentrations produced synergistic cytotoxicity with ABCB1 and ABCG2 substrate chemotherapy drugs and enhanced apoptosis induced by these drugs, including daunorubicin, mitoxantrone, topotecan, and flavopiridol, in cells overexpressing these transport proteins. Combinations of ponatinib and chemotherapy drugs warrant further testing.
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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.