RO-31-8220
RO-31-8220 性质
| 储存条件 | 2-8°C |
|---|---|
| 溶解度 | DMSO:52.77(最大浓度 mg/mL);95.31(最大浓度 mM) DMF:25.0(最大浓度 mg/mL);45.15(最大浓度 mM) DMF:PBS ( pH 7.2) (1:9):0.1(最大浓度 mg/mL);0.18(最大浓度 mM) 乙醇:2.77(最大浓度 mg/mL);5.0(最大浓度 mM) |
| 形态 | 红色固体 |
| 颜色 | 红色 |
| 生物来源 | synthetic (organic) |
| 水溶解性 | water: 1mg/mL DMSO: 100mg/mL |
| InChIKey | SAWVGDJBSPLRRB-UHFFFAOYSA-N |
| SMILES | CS(O)(=O)=O.Cn1cc(C2=C(C(=O)NC2=O)c3cn(CCCSC(N)=N)c4ccccc34)c5ccccc15 |
RO-31-8220 用途与合成方法
|
PKC-α 5 nM (IC 50 ) |
PKC-βI 24 nM (IC 50 ) |
PKC-βII 14 nM (IC 50 ) |
PKC-γ 27 nM (IC 50 ) |
PKC-ε 24 nM (IC 50 ) |
Rat Brain PKC 23 nM (IC 50 ) |
MAPKAP-K1b 3 nM (IC 50 ) |
MSK1 8 nM (IC 50 ) |
S6K1 15 nM (IC 50 ) |
GSK3β 38 nM (IC 50 ) |
Ro 31-8220 mesylate is a potent PKC inhibitor, with IC 50 s of 5, 24, 14, 27, 24 and 23 nM for PKCα, PKCβI, PKCβII, PKCγ, PKCε and rat brain PKC, respectively. Ro 31-8220 also significantly inhibits MAPKAP-K1b, MSK1, S6K1 and GSK3β (IC 50 s, 3, 8, 15, and 38 nM, respectively), with no effect on MKK3, MKK4, MKK6 and MKK7. Moreover, Ro 31-8220 directly suppresses voltage-dependent Na + channels. Ro 31-8220 (1 μM) is neuroprotective against paraoxon-induced neuronal cell death in cerebellar granule neurons, blocks paraoxon-induced caspase-3 activity, and reduces the paraoxon-induced increase in phospho-PKC pan levels.
Ro 31-8220 (6 mg/kg/d, s.c.) is well tolerated, and has half-life of 5.7 hours in mice. Ro 31-8220-treated MLP −/− mice show a dramatic rescue in fractional shortening after treatment for 6 weeks, but the WT mice shows no change.
