MDM2 and cancer: Adding 1 μM M3541, a concentration previously shown to inhibit over 80% of ATM autophosphorylation in response to ionizing radiation in multiple cancer cell lines (16, 23), to the combination of calicheamicin and M3814 in MV4-11 cells abrogated the enhancing effect of M3814 on p53 targets, p21, Mdm2, and Puma, bringing them close to untreated levels at 6 h and still significantly reduced relative to the calicheamicin/M3814 combination at 24 h (Figure 2C).