Figure 1

Compound 1 (Cmpd 1; Cmpd A in Ref. 34) is a potent, cell-permeable dual inhibitor of PKCα and PKCβ with a good selectivity profile. (a) Half-maximal inhibitory concentration (IC50) of Cmpd 1 against PKC family members in recombinant enzyme assays. (b) Kinome tree of selectivity profiling of Cmpd 1 against a panel of 119 kinases. The original kinome tree was taken from Ref.68. The percent inhibition by Cmpd 1 at 1 micromolar (µM) testing concentration is color coded, ranging from 0% inhibition (darker green) to 100% inhibition (darker red), with 50% inhibition displayed in yellow. All kinases with > 50% inhibition are labeled. (c) Percent inhibition by Cmpd 1 in a cell-based assay system using HEK293 cells overexpressing PKCβ2 that produce IL-8 in response to the PKC activator phorbol 12-myristate 13-acetate (PMA; representative experiment shown). Error bars here and in subsequent figures are −/+ standard deviation (SD).