Assay for ATR Kinase Activity

Reference #:

1998-011

Inventors/Contributors

Robert T. Abraham, Ph.D., Randal S. Tibbetts, Ph.D.

Description

Integrity of the genome is monitored at multiple cell-cycle check points throughout the cell cycle. Following DNA damage, these checkpoints activate signal transduction cascades that arrest the progression through the cell cycle to allow repair of the damaged DNA or initiation of apoptosis. The ATR protein is one of four mammalian members of the phosphatidylinositol kinase-related kinase (PIKK) family, all of which function in regulation of the cell cycle. Cells deficient in ATR kinase activity are more sensitive to ionizing radiation than normal. Thus, inhibition of ATR kinase activity sensitizes tumor cells to radiotherapy and chemotherapy. Drugs that inhibit ATR kinase could be used clinically in combination with radiation therapy and/or chemotherapy to enhance the tumor cell kill achieved with such agents. Inhibition of ATR contributes to radiosensitization and chemotherapy, making this a superb target for small molecule inhibitors. The ATR gene product is a potential target for the development of anti-cancer agents. These investigators have devised a substrate-based assay for the measurement of ATR-Kinase inhibitors. An ATR kinase assay would be essential to any drug-discovery program directed towards identifying inhibitors of ATR. As such, this assay could be used to study the regulation of ATR kinase activity which could lead to development of novel therapeutic agents. The ATR assay could be adapted easily into a high-throughput format.

Patent Status

None