ArticleCancers2020
Ensartinib (X-396) Effectively Modulates Pharmacokinetic Resistance Mediated by ABCB1 and ABCG2 Drug Efflux Transporters and CYP3A4 Biotransformation Enzyme.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Unmasking the common enemy: drug resistance mechanisms across three different EGFR inhibitor generations are associated with co-targetable alterations in extracellular matrix signaling.Cell communication and signaling : CCS · 2026Article
- Development and Validation of a UPLC-MS/MS Method for Simultaneous Quantification of Ensartinib and Its Major Metabolite M465 in Rat Plasma and Application to Pharmacokinetic Studies.Drug design, development and therapy · 2026Article
- Mechanistic study of pexidartinib-induced toxicity in human hepatic cells.Chemico-biological interactions · 2025Article
- 7-Hydroxycannabidiol and 7-carboxycannabidiol induced cytotoxicity via apoptosis and endoplasmic reticulum stress in human hepatic cells.Archives of toxicology · 2025Article
- Novel Steroidal[17,16-Molecules (Basel, Switzerland) · 2023Article
- Study of the roles of cytochrome P450 (CYPs) in the metabolism and cytotoxicity of perhexiline.Archives of toxicology · 2022Article
- Encorafenib Acts as a Dual-Activity Chemosensitizer through Its Inhibitory Effect on ABCC1 Transporter In Vitro and Ex Vivo.Pharmaceutics · 2022Article
- Talazoparib Does Not Interact with ABCB1 Transporter or Cytochrome P450s, but Modulates Multidrug Resistance Mediated by ABCC1 and ABCG2: An in Vitro and Ex Vivo Study.International journal of molecular sciences · 2022Article
- P-glycoprotein Mediates Resistance to the Anaplastic Lymphoma Kinase Inhiitor Ensartinib in Cancer Cells.Cancers · 2022Article
- Tepotinib Inhibits Several Drug Efflux Transporters and Biotransformation Enzymes: The Role in Drug-Drug Interactions and Targeting Cytostatic Resistance In Vitro and Ex Vivo.International journal of molecular sciences · 2021Article
- Roles of CYP3A4, CYP3A5 and CYP2C8 drug-metabolizing enzymes in cellular cytostatic resistance.Chemico-biological interactions · 2021Article
- Characterization of cytochrome P450s (CYP)-overexpressing HepG2 cells for assessing drug and chemical-induced liver toxicity.Journal of environmental science and health. Part C, Toxicology and carcinogenesis · 2021Article
- Binding mode analysis of ABCA7 for the prediction of novel Alzheimer's disease therapeutics.Computational and structural biotechnology journal · 2021Article
- OTS964, a TOPK Inhibitor, Is Susceptible to ABCG2-Mediated Drug Resistance.Frontiers in pharmacology · 2021Article
- Current Targeted Therapies for the Fight against Non-Small Cell Lung Cancer.Pharmaceuticals (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Ensartinib (X-396) is a promising tyrosine kinase inhibitor currently undergoing advanced clinical evaluation for the treatment of non-small cell lung cancer. In this work, we investigate possible interactions of this promising drug candidate with ATP-binding cassette (ABC) drug efflux transporters and cytochrome P450 biotransformation enzymes (CYPs), which play major roles in multidrug resistance (MDR) and pharmacokinetic drug-drug interactions (DDIs). Accumulation studies showed that ensartinib is a potent inhibitor of ABCB1 and ABCG2 transporters. Additionally, incubation experiments with recombinant CYPs showed that ensartinib significantly inhibits CYP3A4 and CYP2C9. Subsequent molecular docking studies confirmed these findings. Drug combination experiments demonstrated that ensartinib synergistically potentiates the antiproliferative effects of daunorubicin, mitoxantrone, and docetaxel in ABCB1, ABCG2, and CYP3A4-overexpressing cellular models, respectively. Advantageously, ensartinib's antitumor efficiency was not compromised by the presence of MDR-associated ABC transporters, although it acted as a substrate of ABCB1 in Madin-Darby Canine Kidney II (MDCKII) monolayer transport assays. Finally, we demonstrated that ensartinib had no significant effect on the mRNA-level expression of examined transporters and enzymes in physiological and lung tumor cellular models. In conclusion, ensartinib may perpetrate clinically relevant pharmacokinetic DDIs and modulate ABCB1-, ABCG2-, and CYP3A4-mediated MDR. The in vitro findings presented here will provide a valuable foundation for future in vivo investigations.
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Registered trials
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.