Mirin is a potent Mre11-Rad50-Nbs1 (MRN) complex inhibitor that prevents MRN-dependent activation of ATM (IC50 =12 μM) without affecting ATM protein kinase activity, and inhibits Mre11-associated exonuclease activity. Consistent with its ability to target the MRN complex, Mirin abolishes the G2/M checkpoint and homology-dependent repair in mammalian cells [1].

Mirin effectively inhibits the phosphorylation of H2AX at an IC50 value of 66 μM and suppresses ATM-dependent phosphorylation of downstream targets Nbs1 and Chk2, as well as MRN-dependent autophosphorylation of ATM at Ser1981, following double-strand breaks (DSBs). Additionally, Mirin induces significant G2 phase arrest at both 50 μM and 100 μM concentrations. At doses ranging from 10-100 μM, Mirin disrupts homology-dependent DNA repair in TOSA4 cells, indicating its potential as a therapeutic agent in targeting DNA repair mechanisms [1]. Furthermore, BRCA2-deficient cells exhibit increased sensitivity to Mirin, highlighting its effectiveness as an Mre11 inhibitor [2].