pevonedistat

Pevonedistat, also known as MLN4924, is an investigational small-molecule inhibitor of the NEDD8-activating enzyme (NAE). By inhibiting NAE, it blocks the neddylation of cullin-RING ligases (CRLs), leading to stabilization of CRL substrates, replication stress, cell-cycle arrest, and apoptosis in cancer cells.

Pevonedistat has been evaluated in phase I and II clinical trials, alone and in combination with other therapies, for a range of malignancies including acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), chronic lymphocytic leukemia (CLL), and various solid tumors. Dosing schedules and regimens have varied across studies. It remains an investigational agent and has not received regulatory approval.

In trials, pevonedistat is generally administered by intravenous infusion on cycles that vary by study; the safety profile has included hematologic and non-hematologic adverse events such as cytopenias, fatigue, nausea, and diarrhea, with incidence dependent on the regimen.

Ongoing research seeks to define optimal combinations, dosing strategies, and patient populations that may benefit from NAE inhibition, as well as to clarify the potential role of pevonedistat within the broader landscape of cancer therapeutics.