MilliporeSigma™ Calbiochem™ NAE Inhibitor, MLN4924

Description

• A cell-permeable AMP mimetic that targets the NEDD8-activating E1 enzyme NAE nucleotide-binding site and undergoes a NAE-catalyzed covalent NEDD8 adduct formation, the adduct in turn acts as a tight-binding, ATP-competitive NAE inhibitor (IC 50 = 4.7nM), exhibiting much reduced or little potency against UAE/UBA1, UBA6/UBE1L2, SAE, ATG7, adenosine receptors A 1 /A 2A /A 2B /A 3 , or a panel of 12 cellular kinases
• Selectively reduces cellular Ubc12-NEDD8, but not Ubc9-SUMO or Ubc10-Ub, thioester formation (IC max = 90nM in HCT-116 cultures in 24 h), resulting in cullin-RING ligases substrates elevation
• Shown to inhibit the growth of various cancer cells both in cultures (IC 50 from 50nM to 1.03μM) in vitro and in murine xenograft models (30 to 60mg/kg via s.c.) in vivo via apoptosis induction.