PF-04577806

PF-04577806 is a potent, selective and ATP competitive PKC inhibitor. PF-04577806 shows potent inhibitory activity towards PKCα, PKCβI, PKCβII, PKCγ, and PKCθ with IC50s of 2.4 nM, 8.1 nM, 6.9 nM, 45.9 nM, and 29.5 nM, respectively. PF-04577806 can reverse retinal vascular leakage in diabetic rats[1].

Signaling Pathways >> Epigenetics >> PKC

Research Areas >> Metabolic Disease

Signaling Pathways >> TGF-beta/Smad >> PKC

PKCα:2.4 nM (IC50)

PKCβI:8.1 nM (IC50)

PKCβII:6.9 nM (IC50)

PKCγ:45.9 nM (IC50)

PKCδ:586 nM (IC50)

PKCθ:29.5 nM (IC50)

PKCε:522 nM (IC50)

PF-04577806 (0.001-10 μM; 10 min) inhibits PKC activity in diabetic rat retinal lysates, with IC50 of 0.18 μM[1]. PF-04577806 (0.12-10 μM; pretreated for 60 min) inhibits phorbol myristate acetate-stimulated phosphorylation of ERK1/2 in Jurkat cells, with an IC50 of 0.28 μM[1]. PF-04577806 (0.001-10 μM; pretreated for 1 h) inhibits phosphorylation of SHP2 in HEK293 cells, with an IC50 of 5.8 nM. PF-04577806 concentration-dependently inhibits interleukin 8 release from phorbol myristate acetate-stimulated HEK293 cells, with an IC50 of 0.12 μM[1]. PF-04577806 (1 μM; 48 h) shows low cytotoxicity against human umbilical vein endothelial cells with remaining cell viability at 100.5% viable[1]. Western Blot Analysis[1] Cell Line: Jurkat T cells Concentration: 0, 0.12, 0.37, 1.11, 3.33, 10.0 μM Incubation Time: Pretreated for 1 hours Result: Showed a dose-dependent decrease in phospho-ERK1/2 but not total ERK1/2.

[1]. Grant S, et, al. Discovery of a novel class of targeted kinase inhibitors that blocks protein kinase C signaling and ameliorates retinal vascular leakage in a diabetic rat model. Eur J Pharmacol. 2010 Feb 10;627(1-3):16-25.