GW 5074

The mammalian Raf kinase family consists of A-Raf and B-Raf and c-Raf (or Raf 1). The c-Raf has been proven an upstream activator of mitogen-activated protein kinase (MAPK), which is an important group of mediators transducing signals from cell surface to nucleus under stimuli including cytokines, growth factors, exogenous pressure and mitogens. The RAF was also proven to be an oncogenic gene that was closely associated with tumorigenesis³. GW5074 is a potent inhibitor of c-Raf with an IC₅₀ value of 9 nM. Treatment with GW5074 for 24 hours prevents LK-induced apoptosis in medium containing LK. Maximal protection against LK-induced apoptosis is observed at 1 μM. The activity of c-Raf immunoprecipitated from cultures treated with GW5074 in LK medium displayed a marked induction. Dispite its inhibition of c-Raf, treatment of neuronal cultures with GW5074 lea to an increase in the phosphorylation of ERK 1/2 suggesting that GW5074 treatment caused the activation of either A-Raf or B-Raf. Mice administered 3-NP display extensive bilateral striatal lesions. This degeneration is completely prevented by GW5074 when administered at a concentration of 5 mg/kg body weight⁴.

溶解方案(细胞实验)

DMSO 中的溶解度 : 100 mg/mL (191.96 mM; 超声助溶 (<60°C); 吸湿的 DMSO 对产品的溶解度有显著影响，请使用新开封的 DMSO)

溶解方案(动物实验)

"方案 一": "请依序添加每种溶剂：10% DMSO 40% PEG300 5% Tween-80 45% SalineSolubility: ≥ 2.5 mg/mL (4.80 mM); 悬浊液 此方案可获得 ≥ 2.5 mg/mL（饱和度未知）的均匀悬浊液，悬浊液可用于口服和腹腔注射。以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；再向上述体系中加入 50 μL Tween-80，混合均匀；然后再继续加入 450 μL 生理盐水 定容至 1 mL。生理盐水的配制：将 0.9 g 氯化钠，溶解于 ddH₂O 并定容至 100 mL，可以得到澄清透明的生理盐水溶液。"