Chk2 is a protein kinase activated in response to DNA double strand breaks. In normal tissues, Chk2 phosphorylates and thereby activates substrates that induce programmed cell death, or apoptosis, via interactions with p53, E2F1, PML proteins. In cancer tissues, where apoptosis is suppressed, Chk2 phosphorylates and inactivates cell cycle checkpoints (via interactions with Cdc25, phosphatases and Brca1 proteins), which allows cancer cells to repair and tolerate DNA damage. Hence, Chk2 inhibitors would be expected to protect normal tissues by reducing apoptosis, and to sensitize cancer cells to DNA-targeted agents.
The National Cancer Institute seeks licensees for small molecule inhibitors of Chk2 for the treatment of cancer.