Definition

An orally bioavailable inhibitor of checkpoint kinase 2 (chk2), with potential antineoplastic and chemopotentiating activities. Upon oral administration, Chk2 inhibitor PHI-101 binds to and inhibits the activity of chk2, which may prevent the repair of DNA damage caused by DNA-damaging agents. This may result in tumor cell apoptosis and potentiate the antitumor efficacies of various chemotherapeutic agents. Chk2, an ATP-dependent serine-threonine kinase, is a key component in the DNA replication-monitoring checkpoint system and is activated by double-stranded breaks (DSBs); activated chk2 is overexpressed by a variety of cancer cell types.