HA-9104 is a potent and selective inhibitor of cullin-5 neddylation via virtually targeting the V30 pocket of UBE2F . HA-9104 binds to UBE2F, reduces its protein levels, and consequently inhibits cullin-5 neddylation. HA-9104 has potent growth suppression and radiosensitizing activities via targeting the UBE2F-CRL5 axis and causing DNA damage, leading to induction of apoptosis and G2/M arrest in lung and pancreatic cancer cells.
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