Mirin is a potent Mre11-Rad50-Nbs1 (MRN) complex inhibitor. Mirin prevents MRN-dependent activation of ATM (IC 50 =12 μM) without affecting ATM protein kinase activity, and it 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 inhibits the phosphorylation of H2AX with an IC 50 of 66 μM. Mirin also inhibits the ATM-dependent phosphorylation of the downstream targets Nbs1 and Chk2 and the MRN-dependent autophosphorylation of ATM at Ser1981 in response to DSBs. Mirin induces a substantial G2 arrest at concentrations of 50 μM and 100 μM. Mirin (10-100 μM) inhibits homology-dependent DNA repair in TOSA4 cells [1]. BRCA2-deficient cells also showed hypersensitivity to the Mre11 inhibitor Mirin [2].