Protein neddylation is a post-translational modification which transfers the ubiquitin-like protein NEDD8 to a lysine residue of the target substrate through a three-step enzymatic cascade and has been considered as a viable target for the development of new therapeutics for cancer. M22 is an...
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Protein neddylation is a post-translational modification which transfers the ubiquitin-like protein NEDD8 to a lysine residue of the target substrate through a three-step enzymatic cascade and has been considered as a viable target for the development of new therapeutics for cancer. M22 is an inhibitor of NEDD8 activating enzyme (NAE) which was discovered by virtual screening of a small molecule library (50,000 compounds) against the active site of NAE. M22 is selective and reversible and inhibits NEDDylation of ubiquitin-conjugating enzyme 12 (UBC12) in a cell-free assay employing recombinant human NAE. It selectively inhibits NEDDylation over SUMOylation and ubiquitination in A549 cells and inhibits their growth (GI 50 = 5.5 µM). It has been shown to inhibit tumor growth in a mouse xenograft model (at 60 mg/kg)
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