Ruboxistaurin

Ruboxistaurin (LY333531) is an orally active, selective PKC beta inhibitor (K_i=2 nM). Ruboxistaurin exhibits ATP dependent competitive inhibition of PKC beta I with an IC₅₀ of 4.7 nM. Ruboxistaurin inhibits PKC beta II with an IC₅₀ of 5.9 nM^[1][2]. IC50 & Target: IC50:4.7 nM and 5.9 nM (PKCβ), K_i: 2 nM (PKCβ)^[1] In Vitro: Ruboxistaurin is a selective and ATP-competitive PKCβ inhibitor, with IC₅₀s of 4.7 and 5.9 nM for PKCβI and PKCβII, shows less potent inhibition on PKCη (IC₅₀, 52 nM), PKCα (IC₅₀, 360 nM), PKCγ (IC₅₀, 300 nM), PKCδ (IC₅₀, 250 nM), and has no effect on PKCζ (IC₅₀, >100 μM)^[1]. Ruboxistaurin (10 and 400 nM) dramatically inhibits glucose-induced monocyte adherence to levels that are not different from baseline adherence of monocytes to endothelial cells under NG conditions. Ruboxistaurin (10 and 400 nM) dose not alter the endothelial expression of adhesion molecules or modify endothelial cell growth^[2]. Ruboxistaurin (LY333531; 10 nM) reduces high-glucose (HG)-induced human renal glomerular endothelial cells (HRGECs) viability, and inhibits the increases in swiprosin-1 in HRGECs incubated with HG^[3]. In Vivo: Ruboxistaurin (1 mg/kg; 8 weeks) markedly reduces GEC apoptosis as well as swiprosin-1 upregulation, and ameliorates renal glomerular injury in the diabetic mice. Ruboxistaurin also potently attenuates the expression of PARP, cleaved-caspase9, cleaved-caspase3, and the Bax/Bcl-2 ratio, in diabetic mice^[3]. Ruboxistaurin (0.1, 1.0, or 10.0 mg/kg; p.o.) dramatically reduces the number of leukocytes trapped in the retinal microcirculation of diabetic rats^[4].