切换导航

SL-327

现货
Catalog No.
A1894
MEK1/2选择性抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 500.00
现货
5mg
¥ 500.00
现货
25mg
¥ 800.00
现货
100mg
¥ 2,400.00
现货

电话: 021-55669583

邮箱: sales@apexbio.cn

全球经销商

Background

SL-327 is a selective inhibitor of MEK1 and MEK2 with IC50 values of 0.18 and 0.22μM,  respectively.
MEK1 and MEK2 (ERK) are a kinase enzyme which phosphorylate mitogen-activated protein kinase (MAPK). Extracellular signal-regulated kinase (ERK) activity is essential for the acquisition of associative learning tasks.
In adult male CD-1 mice, SL-327 inhibited Pp-ERK immunostaining in the nuclei of the cells induced by cocaine. SL-327 pretreatment inhibited c-Fos expression in nuclear and inhibited activation of ERK within all the amygdala, namely LA, BLA, BMP, Ce and MePD [1]. In morphine-pretreated rats, SL-327 increased (58%) the expression of morphine-induced psychomotor sensitization (SW3) and fully prevented the upregulation of p-PEA-15, p-FADD, and p-Akt1 at SW3 [2]. In adult male DBA/2J mice, SL-327 significantly reduced pERK levels by 40% in both the motor cortex and dorsal striatum [3]. In rat model, SL-327 inhibited MAPK/ERK cascade, which prevented LTP-dependent gene induction and CREB and Elk-1 phosphorylation, resulting in rapidly decaying LTP [4].
References:
[1]. Radwanska K, Caboche J, Kaczmarek L. Extracellular signal-regulated kinases (ERKs) modulate cocaine-induced gene expression in the mouse amygdala. Eur J Neurosci, 2005, 22(4): 939-948.
[2]. Ramos-Miguel A, Esteban S, García-Sevilla JA. The time course of unconditioned morphine-induced psychomotor sensitization mirrors the phosphorylation of FADD and MEK/ERK in rat striatum: role of PEA-15 as a FADD-ERK binding partner in striatal plasticity. Eur Neuropsychopharmacol, 2010, 20(1): 49-64.
[3]. Groblewski PA, Franken FH, Cunningham CL. Inhibition of extracellular signal-regulated kinase (ERK) activity with SL327 does not prevent acquisition, expression, and extinction of ethanol-seeking behavior in mice. Behav Brain Res, 2011, 217(2): 399-407.
[4]. Davis S, Vanhoutte P, Pages C, et al. The MAPK/ERK cascade targets both Elk-1 and cAMP response element-binding protein to control long-term potentiation-dependent gene expression in the dentate gyrus in vivo. J Neurosci, 2000, 20(12): 4563-4572.

文献引用

1. White SM, Avantaggiati ML, et al. "YAP/TAZ Inhibition Induces Metabolic and Signaling Rewiring Resulting in Targetable Vulnerabilities in NF2-Deficient Tumor Cells." Dev Cell. 2019 May 6;49(3):425 -443.e9. PMID:31063758
2. Kim JW, Ko MJ, et al. "Social support rescues acute stress-induced cognitive impairments by modulating ERK1/2 phosphorylation in adolescent mice." Sci Rep. 2018 Aug 13;8(1):12003. PMID:30104581

Chemical Properties

StorageStore at -20°C
M.Wt335.35
Cas No.305350-87-2
FormulaC16H12F3N3S
Solubility≥16.75mg/mL in DMSO
Chemical Name(Z)-3-amino-3-(4-aminophenyl)sulfanyl-2-[2-(trifluoromethyl)phenyl]prop-2-enenitrile
SDFDownload SDF
Canonical SMILESC1=CC=C(C(=C1)C(=C(N)SC2=CC=C(C=C2)N)C#N)C(F)(F)F
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

激酶实验 [1]:

结合实验

将裂解物(100μg/样品)在4℃的摇摆平台上与10μg抗MAPKAP激酶-2抗体一起温育。3小时后,加入50 μl蛋白质A/G琼脂糖浆液,并将管在4℃下摇动另外1小时。琼脂糖珠在1500×g离心5分钟后沉淀,用裂解缓冲液洗涤3次,用20 mM Hepes的pH7.0缓冲液洗涤一次。将免疫沉淀重悬于75 μl激酶测定缓冲液,缓冲液含有20 mM Hepes、pH 7.0、5 mM 2-巯基乙醇、10 mM MgCl2、0.1 mg/ml牛血清白蛋白、含有2 μg hsp27通过加入10 μM ATP加10μCi的[γ-33P] ATP(PerkinElmer Life Sciences)引发激酶反应,并在25℃温育30分钟。通过加入Laemmli SDS样品缓冲液终止反应,煮沸 5分钟,在12%Tris-甘氨酸凝胶上电泳,干燥,并使用Molecular Dynamics phosphorimager定量。

动物实验 [2,3]:

动物模型

成年雄性CD-1小鼠,吗啡预处理大鼠

溶解方法

该化合物在DMSO中的溶解度大于16.8 mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。

给药剂量

50 mg/kg,在注射前立即在水和DMSO中1:1稀释,腹腔注射

应用

在成年雄性CD-1小鼠中,腹腔注射SL-327(50 mg/kg)抑制在可卡因诱导的细胞核中Pp-ERK的免疫染色。腹腔注射SL-327(50 mg/kg)预处理抑制核中的c-Fos表达,并抑制所有杏仁核内ERK的活化。在吗啡预处理的大鼠中,腹腔注射SL-327(20 mg/kg)增加(58%)吗啡诱导的精神运动致敏(SW3)的表达,并完全阻止SW3中p-PEA-15、p-FADD和 p-Akt1的上调。

注意事项

由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。

References:

[1]. Scherle P A, Ma W, Lim H, et al. Regulation of Cyclooxygenase-2 Induction in the Mouse Uterus During Decidualization AN EVENT OF EARLY PREGNANCY[J]. Journal of Biological Chemistry, 2000, 275(47): 37086-37092.

[2]. Radwanska K, Caboche J, Kaczmarek L. Extracellular signal‐regulated kinases (ERKs) modulate cocaine‐induced gene expression in the mouse amygdala[J]. European Journal of Neuroscience, 2005, 22(4): 939-948.

[3] Ramos-Miguel A, Esteban S, García-Sevilla J A. The time course of unconditioned morphine-induced psychomotor sensitization mirrors the phosphorylation of FADD and MEK/ERK in rat striatum: role of PEA-15 as a FADD-ERK binding partner in striatal plasticity[J]. European Neuropsychopharmacology, 2010, 20(1): 49-64.

生物活性

Description SL-327是一种选择性的MEK1和MEK2抑制剂,IC50值分别为0.18和0.22 μM。
靶点 MEK1 MEK2        
IC50 0.18 μM 0.22 μM        

质量控制

化学结构

SL-327

相关生物数据

SL-327