DNA-activated protein kinase (DNA-PK; EC 2.7.11.1) plays an important role in responding to agents and extracellular stress that threaten the DNA replication process[1]. It is a nuclear protein serine/threonine kinase that must bind to DNA double-strand breaks (DSB) to be active. The nonhomologous end-joining (NHEJ) pathway is considered the main pathway for DSB repair in mammalian cells, and is initiated by binding of DNA-dependent protein kinase (DNA-PK) regulatory subunits to free DNA ends, followed by recruitment of the DNA-dependent kinase catalytic subunit protein (DNA-PKcs) to DSBs. This assembly results in DNA-PK kinase activation. The DNA-PK complex serves as a platform that holds both DNA ends together and orchestrates DNA processing and ligation[2].DNA-PK inhibiting Axon Ligands™ are also listed in the section of theDNA-damage response.