In summary, we have developed specific and potent small molecule antagonists of the Ubc13-Uev1 interaction that inhibit the enzymatic activity of this heterodimer, K63 polyubiquitylation, and we have shown that one of these molecules produces significant effects in the activation of NF-κB by TNF-α, and in invasiveness and clonogenicity in vitro and tumorigenicity of cancer cells in vivo. This evidence concerns the gene UBE2N and cancer.