ArticleCancer chemotherapy and pharmacology2019
CNS penetration of the CDK4/6 inhibitor ribociclib in non-tumor bearing mice and mice bearing pediatric brain tumors.
Article in Cancer chemotherapy and pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Ribociclib is not a substrate or inhibitor of Oatp1b-mediated uptake in vivo.Cancer chemotherapy and pharmacology · 2026Article
- Multiple patient-derived glioblastoma models reveal synthetic lethality through concurrent PI3K and CDK4/6 inhibition by blocking trans-active cooperation.Neuro-oncology · 2026Article
- Dalpiciclib combined with endocrine therapy for patients with HR+/HER2- metastatic breast cancer: a multicenter real-world study.Therapeutic advances in medical oncology · 2026Article
- Combined Ribociclib and NU7026 administration enhances radio-sensitivity by inhibiting DNA repair in prostate cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Effects of combination therapy of a CDK4/6 and MEK inhibitor in diffuse midline glioma preclinical models.PloS one · 2025Article
- Targeted therapy in pediatric central nervous system tumors: a review from the National Pediatric Cancer Foundation.Frontiers in oncology · 2025Review
- GABAergic neuronal lineage development determines clinically actionable targets in diffuse hemispheric glioma, H3G34-mutant.Cancer cell · 2024Article
- Involvement of the tumour necrosis factor receptor system in glioblastoma cell death induced by palbociclib-heptamethine cyanine dye conjugate.Cell communication and signaling : CCS · 2024Article
- Using the LeiCNS-PK3.0 Physiologically-Based Pharmacokinetic Model to Predict Brain Extracellular Fluid Pharmacokinetics in Mice.Pharmaceutical research · 2023Article
- Invasive Neuromonitoring Modalities in the Pediatric Population.Neurocritical care · 2023Review
- Combination of Ribociclib with BET-Bromodomain and PI3K/mTOR Inhibitors for Medulloblastoma Treatment In Vitro and In Vivo.Molecular cancer therapeutics · 2023Article
- Current Molecular and Clinical Landscape of ATRT - The Link to Future Therapies.Cancer management and research · 2023Review
- Review
- Combination of Ribociclib and Gemcitabine for the Treatment of Medulloblastoma.Molecular cancer therapeutics · 2022Article
- Investigational cyclin-dependent kinase 4/6 inhibitor GLR2007 demonstrates activity against isocitrate dehydrogenase wild-type glioblastoma and other solid tumors in mice xenograft models.Frontiers in oncology · 2022Article
- Cyclin-dependent kinase inhibitors in head and neck cancer and glioblastoma-backbone or add-on in immune-oncology?Cancer metastasis reviews · 2021Review
- Characterization of the Synergistic Inhibition ofInternational journal of molecular sciences · 2020Article
- CDK4/6 Inhibitors in Breast Cancer Treatment: Potential Interactions with Drug, Gene, and Pathophysiological Conditions.International journal of molecular sciences · 2020Review
- Cerebrospinal fluid penetration of targeted therapeutics in pediatric brain tumor patients.Acta neuropathologica communications · 2020Article
- Cyclin-dependent kinase inhibitors in brain cancer: current state and future directions.Cancer drug resistance (Alhambra, Calif.) · 2020Review
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
purposeRibociclib, an orally bioavailable small-molecule CDK4/6 inhibitor is currently undergoing evaluation to treat pediatric central nervous system (CNS) tumors. However, it is crucial that it penetrates the brain and tumor. Thus, the objectives of the present study were to derive a clinically relevant mouse dosage for cerebral microdialysis studies, and to characterize ribociclib CNS penetration in non-tumor bearing mice and in mice bearing DIPGx7 (glioma) cortical allograft tumors.
methodsA plasma pharmacokinetic study of ribociclib (100 mg/kg, orally) was performed in CD1 nude mice bearing glioma cortical allografts to obtain initial plasma pharmacokinetic parameters and to derive D-optimal plasma sampling time-points for microdialysis studies. Using a cerebral microdialysis technique, the extracellular fluid (ECF) disposition of ribociclib was evaluated after a single oral ribociclib dose (100 mg/kg) in non-tumor bearing mice and in mice bearing glioma cortical allografts. A one-compartment plasma model with absorption and ECF compartments were fit to plasma and ECF concentration-time data using a nonlinear mixed effects modeling approach (NONMEM 7.2).
resultsThe mean unbound ribociclib plasma exposure (6812 ng/ml*h) was similar to that observed clinically at recommended dosages in adults. The median ribociclib ECF to plasma partition coefficient (K
conclusionsThe CNS penetration observed was encouraging enough to move ribociclib forward with preclinical efficacy studies in models of pediatric brain tumors.
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