ArticleBritish journal of cancer2013
Identification of human-selective analogues of the vascular-disrupting agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA).
Article in British journal of cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 32 citations in OpenAlex.
- Demystifying the cGAS-STING pathway: precision regulation in the tumor immune microenvironment.Molecular cancer · 2025Review
- The Many Ways to Deal with STING.International journal of molecular sciences · 2023Review
- Identification and Characterization of Small-Molecule IRF3-Dependent Immune Activators for Pharmaceutical Development.ACS chemical biology · 2022Article
- Flavonoid-Inspired Vascular Disrupting Agents: Exploring Flavone-8-Acetic Acid and Derivatives in the New Century.Molecules (Basel, Switzerland) · 2021Review
- STING modulators: Predictive significance in drug discovery.European journal of medicinal chemistry · 2019Review
- Article
- Combination of anti-vascular agent - DMXAA and HIF-1α inhibitor - digoxin inhibits the growth of melanoma tumors.Scientific reports · 2018Article
- Identification of a small molecule that primes the type I interferon response to cytosolic DNA.Scientific reports · 2017Article
- Combining vasculature disrupting agent and Toll-like receptor 7/8 agonist for cancer therapy.Oncotarget · 2017Article
- Advancing host-directed therapy for tuberculosis.Nature reviews. Immunology · 2015Review
- Binding-pocket and lid-region substitutions render human STING sensitive to the species-specific drug DMXAA.Cell reports · 2014Article
- Article
- Anticancer flavonoids are mouse-selective STING agonists.ACS chemical biology · 2013Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundSpecies selectivity of DMXAA (5,6-dimethylxanthenone-4-acetic acid, Vadimezan) for murine cells over human cells could explain in part the recent disappointing phase III trials clinical results when preclinical studies were so promising. To identify analogues with greater human clinical potential, we compared the activity of xanthenone-4-acetic acid (XAA) analogues in murine or human cellular models.
methodsAnalogues with a methyl group systematically substituted at different positions of the XAA backbone were evaluated for cytokine induction in cultured murine or human leukocytes; and for anti-vascular effects on endothelial cells on matrigel. In vivo antitumour activity and cytokine production by stromal or cancer cells was measured in human A375 and HCT116 xenografts.
resultsMono-methyl XAA analogues with substitutions at the seventh and eighth positions were the most active in stimulating human leukocytes to produce IL-6 and IL-8; and for inhibition of tube formation by ECV304 human endothelial-like cells, while 5- and 6-substituted analogues were the most active in murine cell systems.
conclusionXanthenone-4-acetic acid analogues exhibit extreme species selectivity. Analogues that are the most active in human systems are inactive in murine models, highlighting the need for the use of appropriate in vivo animal models in selecting clinical candidates for this class of compounds.
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