| Description | Ruboxistaurin hydrochloride (LY 333531 hydrochloride) is an Isozyme-selective inhibitor of protein kinase C (PKC); competitively and reversibly inhibits PKCβI and PKCβII (IC50 values are 4.7 and 5.9 nM respectively). Selective for PKCβ over other PKC isozymes (IC50values are 0.052, 0.25, 0.30, 0.36, 0.60 and >100 μM for PKCη, -δ, -γ, -α, -ε and -ζ respectively). Exhibits selectivity for PKC over other ATP-dependent kinases, including protein kinase A, casein kinase and src). |
| In vitro | LY333531 strikingly decreases the chance of HUVEC survival and the effect of LY333531 on apoptotic cell death in HUVEC significantly increases compared with the AGEs group. Blockade of PKC-beta up-regulates the expression of Bax and Bad proteins and down-regulates the expression of Bcl-2 protein. Moreover, LY333531 reduces the ratio of Bcl-2/Bax. LY333531 can further prompt AGEs-induced endothelial cells apoptosis. The increased expression of Bax, Bad and decreased expression of Bcl-2 and Bcl-2/Bax ratio are associated with the apoptotic process[3]. |
| In vivo | A significant up-regulation of TGF-b1, Smad2 and Smad3 mRNA expression was observed in diabetic rats, which was alleviated by administration of ruboxistaurin. |
| Cell experiments | HUVECs are seeded into 96-well plates in low glucose DMEM with 10% FBS for 12 h. Afterwards, HUVECs are starved for 12 h and incubated with BSA (200 μg/ml), AGEs (200 μg/ml) and LY333531 (200 nM)+AGEs (200 μg/ml) for 48 h. Then, the medium is replaced with 0.5 mg/ml MTT and at 37 ?C in a 95% air/5% CO2 incubator for 4 h. Finally, the medium containing MTT is aspirated and replaced by dimethyl sulphoxide (DMSO). OD is measured with a Microplate spectrophotometer. AGEs:advanced glycation end products.(Only for Reference) |
| Target activity | PKCη:0.052 μM, PKCβ2:5.9 nM, PKCδ:0.25 μM, PKCγ:0.3 μM, PKCβ1:4.7 nM |
| Synonyms | Ruboxistaurin, LY333531 HCl, LY 333531 hydrochloride, 芦布妥林 |
| molecular weight | 505.01 |
| Molecular formula | C28H28N4O3·HCl |
| CAS | 169939-93-9 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 55 mg/mL (108.91 mM), Sonication is recommended. |
| References | 1. Jirousek MR, et al. J Med Chem. 1996, 39(14):2664-71. 2. Lei S, et al. Diabetes. 2013, 62(7):2318-28. 3. Wang SS, et al. Pharmazie. 2011, 66(11):881-7. |