PF-04577806 is a potent, selective, and ATP competitive inhibitor of the protein kinase C (PKC). It exhibits significant inhibitory activity against various isoforms of PKC, including PKCα, PKCβI, PKCβII, PKCγ, and PKCθ, with IC50 values of 2.4 nM, 8.1 nM, 6.9 nM, 45.9 nM, and 29.5 nM, respectively. Furthermore, PF-04577806 has the ability to reverse retinal vascular leakage in diabetic rats.

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].