Biological Activity
B02 is a cell-permeable pyridinylvinyl-quinazolinone compound that is shown to specifically inhibit human RAD51 (IC50 = 27.4 µM). Does not affect RecA even at much higher concentration (~250 µM). Directly interacts with RAD51 (Kd = 5.6 µM), and disrupts its binding to DNA and nucleoprotein filament formation. Blocks double-strand break-induced homologous recombination and enhances sensitivity of cells to Cisplatin and Mitomycin C . Diminishes co-aggregate formation between RAD51-ssDNA filament.
In Vitro
RAD51 Inhibitor B02 specifically inhibits human RAD51 (IC50=27.4 μM), but not its E. coli homologue RecA (IC50>250 μM)[1]. The combination of B02 with cisplatin has the strongest killing effect on the human breast cancer cells MDA-MB-231[2].
In Vivo
B02 significantly enhances the therapeutic effect of cisplatin on tumor cells in vivo. B02 is tolerated by mice at doses up to 50 mg/kg without obvious body weight loss. No inhibition of tumor growth is observed on mice solely treated by B02. Mice treated with 4 mg/kg cisplatin, however, shows a 33% inhibition of tumor growth. Finally, mice treated with 50 mg/kg B02 and 4 mg/kg cisplatin shows a 66% inhibition of tumor growth[2].
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.