High-throughput assay for G(2) checkpoint inhibitors and identification ofthe structurally novel compound isogranulatimide

Treatment of cancer cells lacking p53 function with G(2) checkpoint inhibit ors sensitizes them to the toxic effects of DNA damage and has been propose d as a strategy for cancer therapy. However, few inhibitors are known, and they have been found serendipitously, We report the development of a G(2) c heckpoint inhibition assay that is suitable for high-throughput screening a nd its application to a screen of 1300 natural extracts. We present the iso lation of a new G(2) checkpoint inhibitor, the structurally novel compound isogranulatimide. In combination with gamma-irradiation, isogranulatimide s electively kills MCF-7 cells lacking p53 function.