Indeed, in all three lung cancer lines and one pancreatic cancer line tested, HA-9104 preferentially inhibited cullin-5 neddylation and caused accumulation of CRL5 substrate NOXA, in both dose- and time-dependent manners, with minor, if any, inhibition of cullins 1-4, the other cullin family members (Fig. 2d, Supplementary Fig. 2d, e). This evidence concerns the gene CUL5 and familial pancreatic carcinoma.