U0126

• 产品编号：CST-9903S      品牌：CST       原厂货号：9903S
• 产品分类：生化试剂 > 生物试剂 > 生物活性小分子 > 抑制剂
• 应用分类：

描述：

U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio] butadiene) 是MEK 1、MEK 2高度选择性抑制剂。与PD98059 #9900相比，U0126对MEK1显示了更高的亲和性。U0126、PD98059以相互排斥的方式结合该酶，暗示了它们有一个共同的结合位点(5)。U0126能抑制MEK1、MEK2，而PD98059对MEK1的抑制性比对MEK2的更强。U0126 (MEK1/2抑制子)以冻干白色粉末状供应。10 mM储存时，5 mg抑制子重悬于1.31 ml DMSO中。甲醇能代替DMSO。分装并与于20ºC保存，避免冷冻/解冻循环。因为这样会损害抑制剂。对于试验中的培养后细胞，我们建议在刺激之前，先将细胞用U0126 10 µM处理30 min-2h（可能有必要使用高浓度的）。该产品只用于体外研究，不能用于人类和动物体中。MEK1、MEK2,也被称为MAPK或Erk激酶，它们是双特异性蛋白激酶，在丝裂原活化蛋白激酶级联反应中发挥作用，控制细胞生长和分化(1-3)。MEK1、MEK2的活化是通过Raf样分子对两个丝氨酸（217 /221位点）的磷酸化而实现的，这两个丝氨酸位点位于亚结构域VIII的活化环内。多种生长因子和细胞因子以及膜去极化和钙内流都能激活MEK1/2(1-4)。组成型活化的MEK1/2能够诱导NIH/3T3细胞的转化和PC-12细胞的分化(4)。MEK蛋白通过将p44、p42 MAPK激酶上位于亚结构域VIII的活化环内的丝氨酸和苏氨酸磷酸化，激活p44、 p42 MAPK激酶。

1. Crews, C.M. et al. (1992) Science 258, 478-480.
2. Alessi, D.R. et al. (1994) EMBO J. 13, 1610-1619.
3. Rosen, L.B. et al. (1994) Neuron 12, 1207-1221.
4. Cowley, S. et al. (1994) Cell 77, 841-852.
5. Favata, M.F. et al. (1998) J Biol Chem 273, 18623-32.

原厂资料：

Description

U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio] butadiene) has been shown to be a highly selective inhibitor of MEK 1 and MEK 2. When compared with PD98059 #9900, U0126 shows a significantly higher affinity for MEK1. U0126 and PD98059 bind to this enzyme in a mutually exclusive fashion suggesting that they share a common binding site (5). U0126 is able to inhibit both MEK1 and MEK2 while PD98059 inhibits MEK1 more potently than MEK2.

Directions for Use

U0126 (MEK1/2 Inhibitor) is supplied as a lyophilized white powder. For 10 mM stock, resuspend 5 mg of the inhibitor in 1.31 ml DMSO. Methanol can be substituted for DMSO. Aliquot and freeze at -20ºC or below to avoid multiple freeze/thaw cycles which can degrade the inhibitor. For experiments with cultured cells, we recommend pretreating the cells with U0126 at 10 µM for 30 minutes to two hours prior to stimulation. (It may be necessary to use higher concentrations.) This product is for in vitro research use only and is not intended for use in humans or animals.

Background

MEK1 and MEK2, also called MAPK or Erk kinases, are dual-specificity protein kinases that function in a mitogen activated protein kinase cascade controlling cell growth and differentiation (1-3). Activation of MEK1 and MEK2 occurs through phosphorylation of two serine residues at positions 217 and 221, located in the activation loop of subdomain VIII, by Raf-like molecules. MEK1/2 is activated by a wide variety of growth factors and cytokines and also by membrane depolarization and calcium influx (1-4). Constitutively active forms of MEK1/2 are sufficient for the transformation of NIH/3T3 cells or the differentiation of PC-12 cells (4). MEK activates p44 and p42 MAP kinase by phosphorylating both threonine and tyrosine residues at sites located within the activation loop of kinase subdomain VIII.

1. Crews, C.M. et al. (1992) Science 258, 478-480.
2. Alessi, D.R. et al. (1994) EMBO J. 13, 1610-1619.
3. Rosen, L.B. et al. (1994) Neuron 12, 1207-1221.
4. Cowley, S. et al. (1994) Cell 77, 841-852.
5. Favata, M.F. et al. (1998) J Biol Chem 273, 18623-32.

注意事项：

Storage: Store lyophilized or in solution at -20°C, desiccated.
In lyophilized form, the chemical is stable for 24 months. Once in
solution, use within 3 months to prevent loss of potency. Aliquot
to avoid multiple freeze/thaw cycles