tcsc0348 Pevonedistat

Pevonedistat (MLN4924) is a potent and selective NEDD8-activating enzyme (NAE) inhibitor with an IC₅₀ of 4.7 nM.

IC50 & Target: IC50: 4.7 nM (NAE)^[1]

In Vitro: Pevonedistat (MLN4924) is a potent inhibitor of NAE, and is selective relative to the closely related enzymes UAE, SAE, UBA6 and ATG7 (IC₅₀=1.5, 8.2, 1.8 and >10 μM, respectively) when evaluated in purified enzyme assays that monitor the formation of E2-UBL thioester reaction products. Pevonedistat (MLN4924) selectively inhibits NAE activity compared to the closely related ubiquitin-activating enzyme (UAE, also known as UBA1) and SUMO-activating enzyme (SAE; a heterodimer of SAE1 and UBA2 subunits), in purified enzyme and cellular assays. MLN4924 exhibits potent cytotoxic activity against a variety of human tumour-derived cell lines^[1].

In Vivo: Pevonedistat (MLN4924) (sc, 10 mg/kg, 30 mg/kg, or 60 mg/kg) inhibits the NEDD8 pathway resulting in DNA damage in Mice bearing HCT-116 xenografts^[1].Pevonedistat (sc, 120 mg/kg) and TNF-α (10 μg/kg) synergistically cause liver damage in SD rats^[2].