ArticleDrug metabolism and disposition: the biological fate of chemicals2018
Brain Distribution of a Novel MEK Inhibitor E6201: Implications in the Treatment of Melanoma Brain Metastases.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- E6201, an intravenous MEK1 inhibitor, achieves an exceptional response in BRAF V600E-mutated metastatic malignant melanoma with brain metastases.Investigational new drugs · 2019Trial
- Review
- MEK Inhibition in Glioblastoma: Current Perspectives and Future Directions.International journal of molecular sciences · 2025Review
- Drug Combinations Targeting FAK and MEK Overcomes Tumor Heterogeneity in Glioblastoma.Pharmaceutics · 2025Article
- How Much is Enough? Impact of Efflux Transporters on Drug delivery Leading to Efficacy in the Treatment of Brain Tumors.Pharmaceutical research · 2023Review
- ABCB1 and ABCG2 Regulation at the Blood-Brain Barrier: Potential New Targets to Improve Brain Drug Delivery.Pharmacological reviews · 2023Review
- Leptomeningeal Metastases in Melanoma Patients: An Update on and Future Perspectives for Diagnosis and Treatment.International journal of molecular sciences · 2023Review
- Systematic in vitro analysis of therapy resistance in glioblastoma cell lines by integration of clonogenic survival data with multi-level molecular data.Radiation oncology (London, England) · 2023Article
- The MEK Inhibitor Trametinib Improves Outcomes following Subarachnoid Haemorrhage in Female Rats.Pharmaceuticals (Basel, Switzerland) · 2022Article
- HSP70 inhibition blocks adaptive resistance and synergizes with MEK inhibition for the treatment of NRAS-mutant melanoma.Cancer research communications · 2021Article
- A preclinical report of a cobimetinib-inspired novel anticancer small-molecule scaffold of isoflavones, NSC777213, for targeting PI3K/AKT/mTOR/MEK in multiple cancers.American journal of cancer research · 2021Article
- Improved In Vitro-In Vivo Correlation by Using the Unbound-Fraction-Adjusted ICPharmaceutical research · 2020Article
- Profiling and Identification of Omeprazole Metabolites in Mouse Brain and Plasma by Isotope Ratio-Monitoring Liquid Chromatography-Mass Spectrometric Method.Life (Basel, Switzerland) · 2020Article
- MEK Inhibition Suppresses Growth of Atypical Teratoid/Rhabdoid Tumors.Journal of neuropathology and experimental neurology · 2020Article
- Mutant ACVR1 Arrests Glial Cell Differentiation to Drive Tumorigenesis in Pediatric Gliomas.Cancer cell · 2020Article
- Drug Concentration Asymmetry in Tissues and Plasma for Small Molecule-Related Therapeutic Modalities.Drug metabolism and disposition: the biological fate of chemicals · 2019Review
- Anti-tumor and anti-metastasis efficacy of E6201, a MEK1 inhibitor, in preclinical models of triple-negative breast cancer.Breast cancer research and treatment · 2019Article
- Melanoma central nervous system metastases: An update to approaches, challenges, and opportunities.Pigment cell & melanoma research · 2019Article
- Barriers to Effective Drug Treatment for Brain Metastases: A Multifactorial Problem in the Delivery of Precision Medicine.Pharmaceutical research · 2018Review
- Drug Transporters in Xenobiotic Disposition and Pharmacokinetic Prediction.Drug metabolism and disposition: the biological fate of chemicals · 2018Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Clinically meaningful efficacy in the treatment of brain tumors, including melanoma brain metastases (MBM), requires selection of a potent inhibitor against a suitable target, and adequate drug distribution to target sites in the brain. Deregulated constitutive signaling of mitogen-activated protein kinase (MAPK) pathway has been frequently observed in melanoma, and mitogen-activated protein/extracellular signal-regulated kinase (MEK) has been identified to be an important target. E6201 is a potent synthetic small-molecule MEK inhibitor. The purpose of this study was to evaluate brain distribution of E6201, and examine the impact of active efflux transport at the blood-brain barrier on the central nervous system (CNS) exposure of E6201. In vitro studies utilizing transfected Madin-Darby canine kidney II (MDCKII) cells indicate that E6201 is not a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp). In vivo studies also suggest a minimal involvement of P-gp and Bcrp in E6201's brain distribution. The total concentrations in brain were higher than in plasma, resulting in a brain-to-plasma AUC ratio (Kp) of 2.66 in wild-type mice. The brain distribution was modestly enhanced in
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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.