Activation of nuclear transcription factor κB (NF-κB) by chemotherapeutic agents was found to protect cells from apoptosis. In light of its central role in regulating the cellular resistance to apoptotic agents, inhibition of NF-κB-mediated gene transcription may sensitize tumor cells to chemotherapeutic agents and enhance their efficacy. We describe herein a noncytotoxic imidazoline scaffold that sensitizes leukemia T cells to the chemotherapeutic agent camptothecin. No significant induction of apoptosis was found when cells were treated with the imidazoline; however, pretreatment of cells with this agent resulted in a drastic enhancement in efficacy of camptothecin (∼75-fold). Elucidation of the potential cellular mechanism revealed that the imidazoline prevents nuclear translocation of NF-κB. These findings indicate that inhibition of NF-κB by this imidazoline may present improved strategies in the chemotherapeutic treatment of cancer.