ArticleCancer letters2015
The vascular disrupting activity of OXi8006 in endothelial cells and its phosphate prodrug OXi8007 in breast tumor xenografts.
Article in Cancer letters, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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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
18 citing papers in PubMed.
- Benzosuberene and Tetracyclic Analogues as Colchicine Site Inhibitors of Tubulin Polymerization.ACS medicinal chemistry letters · 2025Article
- Evaluating Therapeutic Efficacy of the Vascular Disrupting Agent OXi8007 Against Kidney Cancer in Mice.Cancers · 2025Article
- Drug-Linker Constructs Bearing Unique Dual-Mechanism Tubulin Binding Payloads Tethered through Cleavable and Non-Cleavable Linkers.Tetrahedron · 2025Article
- Design, Synthesis and Biological Evaluation of 2-Phenyl Indole Analogues of OXi8006 as Colchicine Site Inhibitors of Tubulin Polymerization and Vascular Disrupting Agents.Bioorganic & medicinal chemistry · 2025Article
- Application of Chlorosulfonyl Isocyanate (CSI) in the Synthesis of Fused Tetracyclic Ketone Ring Systems.The Journal of organic chemistry · 2024Article
- Synthesis and biological evaluation of structurally diverse 6-aryl-3-aroyl-indole analogues as inhibitors of tubulin polymerization.European journal of medicinal chemistry · 2024Article
- Synthesis of the Hypoxia-Inducible Factor-2Tetrahedron letters · 2023Article
- Structure Guided Design, Synthesis, and Biological Evaluation of Oxetane-Containing Indole Analogues.Bioorganic & medicinal chemistry · 2023Article
- SB226, an inhibitor of tubulin polymerization, inhibits paclitaxel-resistant melanoma growth and spontaneous metastasis.Cancer letters · 2023Article
- Boron Trifluoride Etherate Promoted Regioselective 3-Acylation of Indoles with Anhydrides.Molecules (Basel, Switzerland) · 2022Article
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- Non-Invasive Evaluation of Acute Effects of Tubulin Binding Agents: A Review of Imaging Vascular Disruption in Tumors.Molecules (Basel, Switzerland) · 2021Review
- Bioreductively Activatable Prodrug Conjugates of Combretastatin A-1 and Combretastatin A-4 as Anticancer Agents Targeted toward Tumor-Associated Hypoxia.Journal of natural products · 2020Article
- A Review on Curability of Cancers: More Efforts for Novel Therapeutic Options Are Needed.Cancers · 2019Review
- Synthesis of dihydronaphthalene analogues inspired by combretastatin A-4 and their biological evaluation as anticancer agents.MedChemComm · 2018Article
- Desacetylvinblastine Monohydrazide Disrupts Tumor Vessels by Promoting VE-cadherin Internalization.Theranostics · 2018Article
- The Novel Antitubulin Agent TR-764 Strongly Reduces Tumor Vasculature and Inhibits HIF-1α Activation.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
This study describes the vascular disrupting ability and the mechanism of action of the indole-based tubulin-binding compound, OXi8006, and its water-soluble phosphate prodrug OXi8007. Treatment of rapidly proliferating human umbilical vein endothelial cells (HUVECs), used as a model for the tumor vasculature, with OXi8006 or OXi8007, caused potent microtubule disruption followed by extensive reorganization of the cytoskeletal network. The mechanism of action involved an increase in focal adhesion formation associated with an increase in phosphorylation of both non-muscle myosin light chain and focal adhesion kinase. These effects were dramatically diminished by an inhibitor of RhoA kinase, a downstream effector of RhoA. Cell cycle blockade at G2/M and cytotoxicity toward rapidly proliferating HUVECs were also observed. Capillary-like networks of HUVECs were disrupted by the action of both OXi8006 and OXi8007. The prodrug OXi8007 exhibited potent and rapid dose-dependent antivascular activity assessed by dynamic bioluminescence imaging (BLI) in an MDA-MB-231-luc breast cancer xenograft mouse model. By 6 hours post treatment, over 93% of the BLI signal was abolished with only a slight recovery at 24 hours. These findings were confirmed by histology. The results from this study demonstrate that OXi8007 is a potent vascular disrupting agent acting through an anti-microtubule mechanism involving RhoA.
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Registered trials
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