Ecrins Thérapeutics SAS

Background: New chemotherapy drugs should be investigated to improve survival of patients with advanced bladder cancer.Here, we report the synthesis and evaluation of AG11, a new flavanone derivative obtained through cyclization of its chalcone precursor CB11.Materials and Methods: The effect of AG11 on cell viability was evaluated by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay and apoptotic cell death was analyzed by flow cytometry.Finally, the effect of AG11 on tubulin polymerization in vitro and microtubule distribution across the cells was investigated.Results: AG11 was found to have an IC₅₀ (half-maximal inhibitory concentration) of 4.6 μM and its inhibitory effect on RT4 cells proliferation is associated with a cell-cycle arrest in G₂+M phases followed by apoptosis after a 48 h treatment.AG11 prevented polymerization of purified tubulin in a concentration-dependent manner in vitro and disrupted mitotic spindle formation in cells.Conclusion: AG11 appears to be an attractive scaffold for further development of a structurally simpler new anti-microtubule agents.