Myr-ZIP (Synonyms: Myristoylated-ZIP, Myristoylated Zeta-Pseudosubstrate Inhibitory Peptide, Myr-Ser-Ile-Tyr-Arg-Arg-Gly-Ala-Arg-Arg-Trp-Arg-Lys-Leu, Myr-SIYRRGARRWRKL-OH, Ζeta Inhibitory Peptide)

Myr-ZIP is a cell-permeable inhibitor of the constitutively active protein kinase C (PKC) isoform PKMζ (K_i = 0.076-2.11 µM).^1,2 It also inhibits PKCα when used at a concentration of 10 µM.³ Myr-ZIP (5 µM) prevents PKC translocation to the plasma membrane induced by ionomycin in HEK293 cells expressing A-kinase anchor protein 79 (AKAP79). Myr-ZIP inhibits the conditioned place preference response to morphine in rats when administered intracranially into the nucleus accumbens core at doses of 10 and 30 nmol/0.5 µl per side.⁴

1.Yao, Y., Shao, C., Jothianandan, D., et al.Matching biochemical and functional efficacies confirm ZIP as a potent competitive inhibitor of PKMζ in neuronsNeuropharmacology64(1)37-44(2013) 2.Lee, A.M., Kanter, B.R., Wang, D., et al.Prkcz null mice show normal learning and memoryNature493(7432)419-419(2013) 3.Bogard, A.S., and Tavalin, S.J.Protein kinase C (PKC)ζ pseudosubstrate inhibitor peptide promiscuously binds PKC family isoforms and disrupts conventional PKC targeting and translocationMol. Pharmacol.88(4)728-735(2015) 4.Li, Y.-q., Xue, Y.-x., He, Y.-y., et al.Inhibition of PKMzeta in nucleus accumbens core abolishes long-term drug reward memoryJ. Neurosci.31(14)5436-5446(2011)