Experiments with a number of carcinoma cell lines have shown that RGB-286638 is a potent radiation sensitizer in all cell lines tested, including breast cancer cell lines, prostate cancer cell lines, neuroblastoma cell lines, and lung cancer cell lines. Potent radiation sensitization was seen in multiple cell lines, where a nearly 50% enhancement of radiation dose was achieved when the compound was added to cells. We have demonstrated that these effects correlate with increased presence of double stranded DNA breaks in treated cells, and with slower repair of these breaks. Experiments on the mechanism of death suggest that cells die predominantly by mitotic catastrophe, as is typical for radiation-induced cell death. The effects of RGB-286638 with radiation are also being tested in a mouse xenograft tumor model. We have begun preparing these results for publication.This compound holds great promise for use in humans.
