NU7441

NU7441 is a small-molecule inhibitor of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a serine/threonine kinase essential for the non-homologous end joining (NHEJ) pathway of repairing DNA double-strand breaks. NU7441 directly inhibits the ATPase activity of DNA-PKcs, thereby blocking phosphorylation events required for end-joining and chromosomal repair.

Potency and selectivity: In biochemical assays, NU7441 exhibits low nanomolar potency against DNA-PKcs and shows substantially reduced activity against ATM, ATR, and class I PI3K isoforms, though off-target inhibition can occur at higher concentrations. Its selectivity profile has been described as favorable in early characterizations, but care is advised when interpreting results at micromolar concentrations due to potential off-target effects.

Applications: NU7441 is used as a research tool to study the role of DNA-PK in the DNA damage response, to investigate the contribution of NHEJ to repair, and to examine radiosensitization and chemosensitization in cell culture and animal models. It has been employed to explore synthetic lethality with other DNA repair defects and in combination with other inhibitors such as PARP inhibitors or replication stress agents.

Limitations: NU7441 is not approved for clinical use and is used only as a laboratory reagent. As with many small-molecule inhibitors, results can be influenced by off-target effects and compound stability. Typical in vitro usage ranges from tens of nanomolar to low micromolar concentrations, with higher doses increasing the risk of non-specific effects.