KU-60019

**KU-60019** is a potent, selective, and cell-permeable small molecule inhibitor of the kinase **ataxia-telangiectasia mutated (ATM)**, with an IC₅₀ of 6.3 nM, demonstrating approximately 270-fold and 1600-fold higher selectivity over the related kinases DNA-PKcs and ATR, respectively[4][10][12][11]. ATM is a serine/threonine protein kinase that responds to DNA double-strand breaks and regulates cell cycle checkpoints, DNA repair, and apoptosis. KU-60019 blocks ATM signaling by inhibiting phosphorylation of ATM substrates such as p53, H2AX, and CHK2, thereby reducing DNA repair, cell cycle checkpoint activation, and promoting cell death upon DNA damage[4][3]. KU-60019 has been shown to radiosensitize cancer cells (notably glioma and breast cancer) and enhance the effectiveness of chemotherapy agents and immunotherapies by interfering with DNA repair mechanisms and survival pathways, including AKT and MEK/ERK signaling[1][2][3][4][7][9]. Developed for preclinical research, it is used as a proof-of-concept molecule for targeting ATM in cancer therapy, especially in combination with radiotherapy, chemotherapy, and immunotherapy[4][7].