A novel p53-activating tryptamine derivative that acts as a HDM2 (Human Double Minute-2) antagonist with potential antineoplastic activity. JNJ-26854165 inhibits the binding of the HDM2–p53 complex to the proteasome, blocking the degradation of p53. It displays potent anti-proliferative and apoptosis-inducing activity in a broad range of p53 wild type and mutant tumor models.