ArticleJournal of molecular neuroscience : MN2003
Overcoming the blood-brain barrier to taxane delivery for neurodegenerative diseases and brain tumors.
Article in Journal of molecular neuroscience : MN, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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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
15 citing papers in PubMed, 50 citations in OpenAlex.
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- Preclinical modeling in glioblastoma patient-derived xenograft (GBM PDX) xenografts to guide clinical development of lisavanbulin-a novel tumor checkpoint controller targeting microtubules.Neuro-oncology · 2022Article
- Therapeutic avenues for cancer neuroscience: translational frontiers and clinical opportunities.The Lancet. Oncology · 2022Review
- Four decades of chemotherapy-induced cognitive dysfunction: comprehensive review of clinical, animal and in vitro studies, and insights of key initiating events.Archives of toxicology · 2022Review
- 6-MOMIPP, a novel brain-penetrant anti-mitotic indolyl-chalcone, inhibits glioblastoma growth and viability.Cancer chemotherapy and pharmacology · 2019Article
- Establishment of a Human iPSC- and Nanofiber-Based Microphysiological Blood-Brain Barrier System.ACS applied materials & interfaces · 2018Article
- Back to the tubule: microtubule dynamics in Parkinson's disease.Cellular and molecular life sciences : CMLS · 2017Review
- Targeting potassium channels for increasing delivery of imaging agents and therapeutics to brain tumors.Frontiers in pharmacology · 2013Article
- Examination of blood-brain barrier (BBB) integrity in a mouse brain tumor model.Journal of neuro-oncology · 2013Article
- Enhancing the efficacy of drug-loaded nanocarriers against brain tumors by targeted radiation therapy.Oncotarget · 2013Article
- Microtubule stabilizing agents as potential treatment for Alzheimer's disease and related neurodegenerative tauopathies.Journal of medicinal chemistry · 2012Review
- A dicarboxylic fatty acid derivative of paclitaxel for albumin-assisted drug delivery.Journal of pharmaceutical sciences · 2012Article
- Trends in the molecular pathogenesis and clinical therapeutics of common neurodegenerative disorders.International journal of molecular sciences · 2009Review
- Intestinal absorption of novel-dipeptide prodrugs of saquinavir in rats.International journal of pharmaceutics · 2007Article
- Functional characterization of peptide transporters in MDCKII-MDR1 cell line as a model for oral absorption studies.International journal of pharmaceutics · 2007Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The blood-brain barrier (BBB) effectively prevents microtubule (MT)-stabilizing drugs from readily entering the central nervous system (CNS). A major limiting factor for microtubule-stabilizing drug permeation across the BBB is the active efflux back into the circulation by the overexpression of the multidrug-resistant gene product 1 (MDR1) or P-glycoprotein (P-gp). This study has focused on strategies to overcome P-gp-mediated efflux of Taxol analogs, MT-stabilizing agents that could be used to treat brain tumors and, potentially, neurodegenerative diseases such as Alzheimer's disease. However, taxol is a strong P-gp substrate that limits its distribution across the BBB and therapeutic potential in the CNS. We have found that addition of a succinate group to the C-10 position of paclitaxel (Taxol) results in an agent, Tx-67, with reduced interactions with P-gp and enhanced permeation across the BBB in both in vitro and in situ models. Our studies demonstrate the feasibility of making small chemical modifications to Taxol to generate analogs with reduced affinity for the P-gp but retention of MT-stabilizing properties, i.e., a taxane that may reach and treat therapeutic targets in the CNS.
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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.