HA-9104 is a specific small molecule inhibitor of E2 conjugating enzyme UBE2F with IC50 of 33.29 uM for inhibition of cullin-5 neddylation, abrogates UBE2F-NEDD8 thioester formation and inhibits cullin-5 neddylation.
HA-9104 inhibits cullin-5 neddylation via blocking the formation of UBE2F-NEDD8 thioester.
HA-9104 reduces UBE2F protein levels to selectively inhibits cullin-5 neddylation, causes accumulation of CRL5 substrate NOXA, in both dose- and time-dependent manners, with little to no effect on cullins 1-4, the other cullin family members.
HA-9104 reduces UBE2F protein via a mechanism of neither enhanced degradation, nor reduced translation.
HA-9104 significantly induces apoptosis via NOXA accumulation, induces G2/M arrest and triggers replication stress to delay DNA damage repair.
HA-9104 suppresses cancer cell growth and sensitizes cancer cells to radiation, inhibits in vivo tumor growth alone or in combination with radiation.