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 (IC50 = 4.7nM), exhibiting much reduced or little potency against UAE/UBA1, UBA6/UBE1L2, SAE, ATG7, adenosine receptors A1/A2A/A2B/A3, or a panel of 12 cellular kinases. Selectively reduces cellular Ubc12-NEDD8, but not Ubc9-SUMO or Ubc10-Ub, thioester formation (ICmax = 90nM in HCT-116 cultures in 24h), resulting in cullin-RING ligases substrates elevation. Shown to inhibit the growth of various cancer cells both in cultures (IC50 from 50nM to 1.03uM) in vitro and in murine xenograft models (30 to 60mg/kg via s.c.) in vivo via apoptosis induction.
Solubility:DMSO (100mg/ml). Use only fresh DMSO for reconstitution.
Storage and Stability:Powder may be stored at 4°C. Do not freeze. Stable for 6 months after receipt at 4°C. Reconstitute with DMSO. For maximum recovery of product, centrifuge the original vial prior to removing the cap.
