GF 109203X is a selective inhibitor of protein kinase C, selective for the α and β1 isoforms with IC50 values of 0.0084, 0.0180, 0.210, 0.132, and 5.8μM for α, β1, δ, ε and ζ isoforms of protein kinase C respectively[1]. GF 109203X selectively inhibits over MLCK, PKG, and PKA (IC50 values are 0.6, 4.6, and 33μM respectively). GF 109203X is also an antagonist at the 5-HT3 receptor with a Ki of 29.5nM[2]. GF 109203X shows an anti-inflammatory effect targeting human neutrophils in vivo[3].
In vitro, inhibition of PKC by GF 109203X (1μM; 1h) activates GSK-3, whereas activation of PKC by phorbol-12,13-butyrate inhibits GSK-3[4]. Inhibition of protein kinase C with GF 109203X (3μM; 6h)resulted in concentration-dependent but partial inhibition of [(35)S]sulfate incorporation accompanied by a reduction in the particle size of biglycan and decorin[5]. PKC inhibitor GF 109203X (1μM; 5min) did not inhibit KCl-induced tonic force and myosin light chain (MLC) phosphorylation in rabbit artery[6].
In vivo, ventricular co-injection of wortmannin and GF 109203X (WT/GFX) (10μM and 100μM; once; i.p) can induce tau hyperphosphorylation and memory impairment of rats through activation of GSK-3[7]. GF 109203X (0.3pg/site; once; local injection) impaired memory reconsolidation in the presence of spermidine (200pmol/site)[8].
References:
[1] Toullec, D et al. “The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C.” *The Journal of biological chemistry* vol. 266,24 (1991): 15771-81.
[2] Coultrap, S J et al. “Competitive antagonism of the mouse 5-hydroxytryptamine3 receptor by bisindolylmaleimide I, a "selective" protein kinase C inhibitor.” *The Journal of pharmacology and experimental therapeutics* vol. 290,1 (1999): 76-82.
[3] Cabanis, A et al. “Effect of the protein kinase C inhibitor GF 109 203X on elastase release and respiratory burst of human neutrophils.” *General pharmacology* vol. 27,8 (1996): 1409-14. doi:10.1016/s0306-3623(96)00053-5
[4] Wang, Ze-Fen et al. “Effects of endogenous beta-amyloid overproduction on tau phosphorylation in cell culture.” *Journal of neurochemistry* vol. 98,4 (2006): 1167-75. doi:10.1111/j.1471-4159.2006.03956.x
[5] Ivey, Melanie E, and Peter J Little. “Thrombin regulates vascular smooth muscle cell proteoglycan synthesis via PAR-1 and multiple downstream signalling pathways.” *Thrombosis research* vol. 123,2 (2008): 288-97. doi:10.1016/j.thromres.2008.04.019
[6] Urban, Nicole H et al. “K+ depolarization induces RhoA kinase translocation to caveolae and Ca2+ sensitization of arterial muscle.” *American journal of physiology. Cell physiology* vol. 285,6 (2003): C1377-85. doi:10.1152/ajpcell.00501.2002
[7] Liu, Shi Jie et al. “Overactivation of glycogen synthase kinase-3 by inhibition of phosphoinositol-3 kinase and protein kinase C leads to hyperphosphorylation of tau and impairment of spatial memory.” *Journal of neurochemistry* vol. 87,6 (2003): 1333-44. doi:10.1046/j.1471-4159.2003.02070.x
[8] Girardi, Bruna Amanda et al. “Spermidine-induced improvement of reconsolidation of memory involves calcium-dependent protein kinase in rats.” *Learning & memory (Cold Spring Harbor, N.Y.)* vol. 23,1 21-8. 15 Dec. 2015, doi:10.1101/lm.039396.115
GF 109203X是蛋白激酶C的选择性抑制剂，对蛋白激酶C的α和β1亚型具有选择性，对α、β1、δ、ε和ζ亚型的IC50值分别为0.0084、0.0180、0.210、0.132和5.8μM。GF 109203X可选择性抑制MLCK、PKG、PKA （IC50分别为0.6, 4.6, and 33μM）[1]。GF 109203X也是5-HT3受体的拮抗剂，Ki值为29.5nM[2]。GF 109203X在体内具有针对人中性粒细胞的抗炎作用[3]。
在体外，GF 109203X (1μM; 1h) 对PKC的抑制作用并激活GSK-3，而phorhol -12,13-butyrate激活PKC则抑制GSK-3[4]。GF 109203X (3μM; 6h) 对蛋白激酶C的抑制作用导致[(35)S]硫酸盐融入的浓度依赖但部分抑制作用，同时导致biglycan和decorin的颗粒大小减小[5]。PKC抑制剂GF 109203X (1μM; 5min) 不抑制KCl诱导的兔动脉强直力和肌球蛋白轻链（MLC）磷酸化[6]。
在体内，wortmannin与GF-109203X (WT/GFX) (10μM and 100μM; 单次; 腹腔注射) 可通过激活GSK-3诱导tau过度磷酸化和大鼠记忆障碍[7]。GF 109203X (0.3pg/site; 单次; 原位注射)损伤在亚精胺（200pmol/site）存在时的记忆巩固[8]。