ArticleNeuro-oncology advances
A brain-penetrant microtubule-targeting agent that disrupts hallmarks of glioma tumorigenesis.
Article in Neuro-oncology advances. 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, 24 citations in OpenAlex.
- Therapeutic potential of colchicine-binding site inhibitors in breast cancer brain metastasis.Cancer letters · 2026Review
- Novel Susceptibility Genes for Sepsis Revealed by a Cross-Tissue Transcriptome-Wide Association Study.Shock (Augusta, Ga.) · 2026Article
- Drug screening for α-synuclein aggregation inhibitors via multimodal graph neural network.Briefings in bioinformatics · 2026Article
- Cellular heterogeneity and therapeutic response profiling of human IDH + glioma stem cell cultures.Scientific reports · 2025Article
- Histone methyltransferase PRDM9 promotes survival of drug-tolerant persister cells in glioblastoma.Nature communications · 2025Article
- Recent Advances in Microtubule Targeting Agents for Cancer Therapy.Molecules (Basel, Switzerland) · 2025Review
- Microtubule-Targeting Agents: Advances in Tubulin Binding and Small Molecule Therapy for Gliomas and Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- AMPA Receptor Modulation in the Treatment of High-Grade Glioma: Translating Good Science into Better Outcomes.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Computational discovery of potential therapeutic agents against brain-eating amoeba (Naegleria fowleri).PloS one · 2025Article
- The Alcatraz-Strategy: a roadmap to break the connectivity barrier in malignant brain tumours.Molecular oncology · 2024Review
- The microtubule targeting agent ST-401 triggers cell death in interphase and prevents the formation of polyploid giant cancer cells.Journal of translational medicine · 2024Article
- Lucanthone, a Potential PPT1 Inhibitor, Perturbs Stemness, Reduces Tumor Microtube Formation, and Slows the Growth of Temozolomide-Resistant Gliomas In Vivo.The Journal of pharmacology and experimental therapeutics · 2024Article
- Intrinsic and Microenvironmental Drivers of Glioblastoma Invasion.International journal of molecular sciences · 2024Review
- A clinically applicable connectivity signature for glioblastoma includes the tumor network driver CHI3L1.Nature communications · 2024Article
- Brain Tumor Networks in Diffuse Glioma.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- Disconnecting multicellular networks in brain tumours.Nature reviews. Cancer · 2022Review
- Synergistic Effects of A Combined Treatment of Glioblastoma U251 Cells with An Anti-miR-10b-5p Molecule and An AntiCancer Agent Based on 1-(3',4',5'-Trimethoxyphenyl)-2-Aryl-1International journal of molecular sciences · 2022Article
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Corrections and comments
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundGlioma is sensitive to microtubule-targeting agents (MTAs), but most MTAs do not cross the blood brain barrier (BBB). To address this limitation, we developed the new chemical entity, ST-401, a brain-penetrant MTA.
methodsSynthesis of ST-401. Measures of MT assembly and dynamics. Cell proliferation and viability of patient-derived (PD) glioma in culture. Measure of tumor microtube (TM) parameters using immunofluorescence analysis and machine learning-based workflow. Pharmacokinetics (PK) and experimental toxicity in mice. In vivo antitumor activity in the RCAS/tv-a PDGFB-driven glioma (PDGFB-glioma) mouse model.
resultsWe discovered that ST-401 disrupts microtubule (MT) function through gentle and reverisible reduction in MT assembly that triggers mitotic delay and cell death in interphase. ST-401 inhibits the formation of TMs, MT-rich structures that connect glioma to a network that promotes resistance to DNA damage. PK analysis of ST-401 in mice shows brain penetration reaching antitumor concentrations, and in vivo testing of ST-401 in a xenograft flank tumor mouse model demonstrates significant antitumor activity and no over toxicity in mice. In the PDGFB-glioma mouse model, ST-401 enhances the therapeutic efficacies of temozolomide (TMZ) and radiation therapy (RT).
conclusionOur study identifies hallmarks of glioma tumorigenesis that are sensitive to MTAs and reports ST-401 as a promising chemical scaffold to develop brain-penetrant MTAs.
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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.