Our group recently developed an Alpha-Screen-based high throughput screen (HTS) assay, and identified a natural compound derived from cotton seed named gossypol that can effectively block neddylation of CUL1 and CUL5 by directly binding to RBX1-CUL1 or SAG-CUL5 complex, respectively.467 In this way, gossypol inhibits cullins neddylation in multiple cancer cell lines but selectively causes accumulation of the CRL1 substrate MCL1, and CRL5 substrate NOXA.467 By inducing the accumulation of NOXA, gossypol induces apoptosis in few cancer cell lines. This evidence concerns the gene CUL5 and cancer.