1-Naphthyl PP1 hydrochloride (1-NA-PP 1 hydrochloride)

1-NA-PP1 is a reversible, cell-permeable inhibitor of Src-family tyrosine kinases that have been mutated, by a single base substitution, to become ‘analog sensitive’ (as), as compared to the wild-type kinase. 1-NA-PP1 was first developed to optimally inhibit v-Src-as1, with an I338G substitution, preferentially over v-Src (IC₅₀ = 1.5 nM versus 1.0 μM, respectively).¹ The homologous mutation in other kinases generated similar analog sensitivity (e.g., IC₅₀ = 1.5 nM for c-Fyn-as1 versus 0.6 μM for c-Fyn; 7.0 nM for c-Abl-as2 versus 0.6 μM for c-Abl; 15 nM for Cdk2-as1 versus 18 μM for Cdk2).² This approach has been used to elucidate functions of several kinases in both mammalian and yeast systems.^2,3,4

1.Bishop, A.C., Kung, C.y., Shah, K., et al.Generation of monospecific nanomolar tyrosine kinase inhibitors via a chemical genetic approachJ. Am. Chem. Soc.121(4)627-631(1999) 2.Bishop, A.C., Ubersax, J.A., Petsch, D.T., et al.A chemical switch for inhibitor-sensitive alleles of any protein kinaseNature407(6802)395-401(2000) 3.Endo, S., Satoh, Y., Shah, K., et al.A single amino-acid change in ERK1/2 makes the enzyme susceptible to PP1 derivativesBiochem. Biophys. Res. Commun.341261-265(2006) 4.Kenski, D.M., Zhang, C., von Zastrow, M., et al.Chemical genetic engineering of G protein-coupled receptor kinase 2J. Biol. Chem.280(41)35051-35061(2005)