Purpose: To evaluate a mitotic inhibitor, ON01910.Na, as a potential chemotherapeutic agent for brain tumors using a series of PK/PD studies, which led to the evaluation of its structural analog, ON013105, a prodrug of the more lipophilic product, ON013100.
Methods: Systemic PK characterization of ON01910 and ON013105 was completed in healthy mice. Using an orthotopic U87 glioma mouse model, brain and brain tumor distribution under steady-state conditions were evaluated for ON01910.Na and ON013105/ON013100; anticancer potential following a multiple-dose schedule of 250 mg/kg/day IP for 7 days was evaluated for ON01910.Na.
Results: ON01910 exhibited low brain and brain tumor distribution with quasi-steady-state brain/plasma (Css(brain)/Css(plasma)) and brain tumor/plasma (Css(brain tumor)/Css(plasma)) concentration ratios of 0.03 ± 0.02 and 0.14 ± 0.08, respectively. Significant antiangiogenic potential and antiproliferative capacity of ON01910 in the intracerebral model was absent. ON013100 showed high brain and brain tumor penetration with Css(brain)/Css(plasma) and Css(brain tumor)/Css(plasma) ratios of 0.92 ± 0.26 and 1.35 ± 0.40, respectively; its prodrug ON013105 showed negligible brain and brain tumor penetration.
Conclusions: ON013105, not ON01910.Na, was identified as a potential anticancer drug candidate for further investigation in brain tumor chemotherapy based on the properties of ON013100.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s11095-012-0780-y | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mapping the topography of spatial gene expression with interpretable deep learning.
Nat Methods
January 2025
Department of Computer Science, Princeton University, Princeton, NJ, USA.
Spatially resolved transcriptomics technologies provide high-throughput measurements of gene expression in a tissue slice, but the sparsity of these data complicates analysis of spatial gene expression patterns. We address this issue by deriving a topographic map of a tissue slice-analogous to a map of elevation in a landscape-using a quantity called the isodepth. Contours of constant isodepths enclose domains with distinct cell type composition, while gradients of the isodepth indicate spatial directions of maximum change in expression.
View Article and Find Full Text PDFComparative proteomic analysis of astrocytoma tissues from patients with and without seizures.
Sci Rep
January 2025
Neurology Unit, Department of Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand.
Astrocytoma is a common type of glioma and a frequent cause of brain tumour-related epilepsy. Although the link between glioma and epilepsy is well established, the precise mechanisms underlying epileptogenesis in astrocytoma remain poorly understood. In this study, we performed proteomic analysis of astrocytoma tissue from patients with and without seizures using mass spectrometry-based techniques.
View Article and Find Full Text PDFContributing factors to postoperative surgical site infections in pituitary neuroendocrine tumors undergoing endonasal transsphenoidal resection.
Sci Rep
January 2025
Department of Neurosurgery, Xinxiang Central Hospital, 56 Jinsui Avenue, Weibin District, Xinxiang, 453000, Henan, China.
Pituitary Neuroendocrine Tumors (PitNETs), often treated via endonasal transsphenoidal resection, present a risk for postoperative surgical site infections (SSIs), including intracranial infections such as meningitis. Identifying the risk factors associated with these infections is crucial for improving surgical outcomes and patient care. A retrospective study was conducted at a medical center from June 2020 to June 2023.
View Article and Find Full Text PDFAescin ameliorates alcohol-induced liver injury. A possible implication of ROS / TNF-alpha / p38MAPK / caspase-3 signalling.
Food Chem Toxicol
January 2025
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Kaferelsheikh University, Kaferelsheikh, Egypt. Electronic address:
Alcoholic liver disease (ALD) is a commonly known liver disease mediated by prolonged alcohol consumption. Aescin is a triterpene saponin that can manage several conditions, including brain trauma, arthritis, venous congestion, stroke, and thrombophlebitis. Even so, studies illustrating the aescin role in ALD are scarce.
View Article and Find Full Text PDFLike, share, and spike: Glioblastoma progenitors influence neuronal excitability at the glioma-neural interface.
Neuron
January 2025
Department of Pathology and Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address:
Writing in Neuron, Zhang et al. identify a subpopulation of glioblastoma cells from patient tumor samples with progenitor-like features that expresses the potassium ion channel KCND2. In mouse and organoid models, these cells enhance neural activity at the glioma-neural interface.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!