ATM-IN-2 is a selective, orally active ATM inhibitor with an IC50 of 4 nM. It demonstrates high kinase selectivity, being over 700 times more selective relative to PIKK family members. ATM-IN-2 exerts its anti-tumor effects and promotes apoptosis by inhibiting ATM phosphorylation and downstream signaling pathways (p53, H2AX). It is applicable for research in solid tumors, such as colon cancer.

ATM:4 nM

ATM-IN-2 (Compound 25a) demonstrates potent inhibitory activity against HEL116 and SW620 cells over 6-7 days with IC50 values of 58.2 and 66.6 nM, respectively, significantly reducing the cells' clonogenic potential. Over a 2-day period, ATM-IN-2 (1-4 μM) enhances the therapeutic effect of Irinotecan by exacerbating G2/M phase arrest and promoting apoptosis, leading to a synergistic antiproliferative effect in HCT116 cells. Additionally, ATM-IN-2 (0.25-2 μM, 4 h) effectively suppresses ATM signaling activation in HCT116 and SW620 cells.

ATM-IN-2 (Compound 25a), administered orally at doses of 15-30 mg/kg for 14-20 days, exhibits synergistic anti-tumor activity with Irinotecan in a mouse xenograft cancer model.