Evaluation of Sydnone-Based Analogues of Combretastatin A-4 Phosphate (CA4P) as Vascular Disrupting Agents for Use in Cancer Therapy
Related Experiment Video
Updated: Feb 4, 2026

Evaluating Vascular Hyperpermeability-inducing Agents in the Skin with the Miles Assay
Published on: June 19, 2018
Andrew W Brown1,2, Toby Holmes2, Matthew Fisher2
1Department of Chemistry, The University of Sheffield, Dainton Building, Brook Hill, Sheffield, S3 7HF, UK.
Abstract:
The combretastatins have attracted significant interest as small-molecule therapies for cancer due to their ability to function as vascular disrupting agents. We have successfully prepared a range of combretastatin analogues that are based on a novel sydnone heterocycle core, and their potential as tubulin binders has been assessed in vitro and in vivo. The most potent candidate was found to disrupt microtubules and affect cellular morphology at sub-micromolar levels. Moreover, it was found to bind reversibly to tubulin and significantly increase endothelial cell monolayer permeability, in a similar manner to combretastatin A4. Surprisingly, the compound did not exhibit efficacy in vivo, possibly due to rapid metabolism.
Related Concept Videos
Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
Targeted Cancer Therapies
There are several types of targeted therapies against...
Phosphate Buffer
Sodium dihydrogen phosphate does not fully dissociate in neutral or acidic solutions. When a strong base, such as sodium hydroxide (NaOH), is introduced into the solution, sodium dihydrogen phosphate...
Seedless Vascular Plants
Roles of Electrolytes: Calcium and Phosphate
The calcium concentration in blood plasma is primarily...
Gene Therapy

