Matching biochemical and functional efficacies confirm ZIP as a potent competitive inhibitor of PKMζ in neurons

► ZIP is a competitive PKMζ inhibitor that blocks PKMζ-mediated synaptic potentiation. ► Chelerythrine is a redox-sensitive PKC inhibitor, effective on PKMζ. ► High levels of PKMζ render standard doses of ZIP and chelerythrine ineffective. ► Overexpression methodologies increase PKMζ 30- to 40-fold over endogenous levels. ► Staurosporine does not inhibit PDK1 phosphorylation of endogenous PKMζ in neurons.