PF-04577806 is a potent, selective, and ATP-competitive inhibitor of protein kinase C (PKC), showing significant inhibitory activity against various PKC isoforms, including PKCα (IC50=2.4 nM), PKCβI (IC50=8.1 nM), PKCβII (IC50=6.9 nM), PKCγ (IC50=45.9 nM), and PKCθ (IC50=29.5 nM). Additionally, it can reverse retinal vascular leakage in diabetic rats.

PKCβI:8.1 nM (IC50), PKCγ:45.9 nM (IC50), PKCθ:29.5 nM (IC50), PKCε:522 nM (IC50), PKCα:2.4 nM (IC50), PKCβII:6.9 nM (IC50), PKCδ:586 nM (IC50)

PF-04577806, at concentrations ranging from 0.001 to 10 μM, demonstrates a diverse range of inhibitory activities in various experimental models. In diabetic rat retinal lysates, it inhibits Protein Kinase C (PKC) activity within 10 minutes, achieving an IC50 value of 0.18 μM[1]. Furthermore, when pretreated for 60 minutes, PF-04577806 at concentrations of 0.12 to 10 μM significantly reduces phorbol myristate acetate-induced phosphorylation of ERK1/2 in Jurkat cells, with an IC50 of 0.28 μM[1]. Similarly, pretreatment with the compound for 1 hour inhibits SHP2 phosphorylation in HEK293 cells across a range of 0.001 to 10 μM, exhibiting a notably low IC50 of 5.8 nM. It also displays a concentration-dependent suppression of interleukin 8 release in HEK293 cells stimulated by phorbol myristate acetate, with an IC50 of 0.12 μM[1]. Besides its inhibitory effects, PF-04577806 shows minimal cytotoxicity towards human umbilical vein endothelial cells at a 1 μM concentration over 48 hours, maintaining cell viability at 100.5%[1]. Western Blot Analysis on Jurkat T cells, over a 1-hour pretreatment with 0 to 10 μM concentrations, reveals a dose-dependent decrease in phospho-ERK1/2 levels without affecting total ERK1/2[1].