Background:

1-NM-PP1 is a C3-modified analog of cell-permeable PP1, acts as a potent and selective inhibitor of protein kinase families [1].

1-NM-PP1 has shown the selective inhibition of protein kinases that have been mutated with the IC50 values of 28 μM, 1.0 μM, 3.4 μM, 29 μM, 24 μM,4.3 nM, 3.2 nM, 120 nM,5 nM and 8 nM for v-Src, c-Fyn, c-Abl, CDK2, CAMKII, v-Src-as1, c-Fyn-as1, cAbl-as2, CDK2-as1 and CAMKII-as1, respectively. 1-NM-PP1 inhibited each of the five target kinases at low nanomolar concentrations with target-specificities ranging from 85-fold to 400-fold measured against the most inhibitable wild-type kinases. In addition, the in vitro study has also revealed that Cdc28-as1 is highly sensitive to 1-NM-PP1 with ATP kinetic Km values of 35 μM and 322 μM, the Kcat values of 132 min-1 and 21.3 min-1, the Kcat/Km values of 3.7 and 0.066, the IC50 values of 22 μM and 0.002 μM for Cdc28/Clb2 and Cdc28-as1/Clb2, respectively [1].

参考文献:
[1] Bishop AC1, Ubersax JA, Petsch DT, Matheos DP, Gray NS, Blethrow J, Shimizu E, Tsien JZ, Schultz PG, Rose MD, Wood JL, Morgan DO, Shokat KM. A chemical switch for inhibitor-sensitive alleles of any protein kinase. Nature. 2000 Sep 21; 407(6802):395-401.