A sulfonamide derivative prevents the infamous tumor suppressor p53 from parking at the mitochondria. This activity could mitigate severe side effects of radiation therapy. p53 is best known for triggering cell suicide by binding directly to DNA. The protein is often inactivated in tumor cells, allowing them to grow uncontrollably. But p53 has many cellular roles, including the ability to initiate cell death by binding to mitochondria and unplugging the organelle's pores. This second kiss of death is activated in healthy blood progenitor cells during γ-radiation therapy, leading to nasty side effects. Inhibiting p53's translocation to the mitochondria with pifithrin-µ (shown) controls p53's bad behavior during γ-radiation without compromising its other essential roles in the cell (Nat. Chem. Bio., DOI:10.1038/nchembio809). "Pifithrin-µ allows pharmacological dissection of one of the major branches of p53 function," says author Andrei V. Gudkov from the Lerner Research Institute, in Cleveland. "There's also great therapeutic potential for this small molecule," comments Alexander I. Zaika of Vanderbilt University Medical Center.