SB 203580
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
SB203580[4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1Himidazole][6]是一种特异性的吡啶咪唑类p38-MAPK (促分裂原活化蛋白激酶)信号通路抑制剂[1] [3]。SB203580与ATP竞争结合ATP结合口袋内部或附近的非保守区域,Ki值为21 nM [3]。在体外,SB203580也可以抑制c-Raf,IC50值为2 mM [4]。
P38 MAPK信号通路使细胞针对一系列外部信号做出相应的反应。在该途径中依次起作用的三个蛋白激酶的核心确保细胞内反应的多样性和特异性[5]。
用30 mM的SB203580处理显著减少L1210/VCR细胞对vincristine的耐受性,使得vincristine的LC50值从3.2036±0.521变为0.5576±0.082 mM。10 mM的SB203580处理轻微改变了耐药指数,使得SB203580在敏感的L1210细胞和耐受细胞中的LC50值分别为39.26±2.2 mM和52.06±7.6 mM [1]。
在体内,在永久性大脑中动脉闭塞之前24小时用SB203580单独给药废除了异氟醚(isoflurane)预处理诱导的神经保护作用。在异氟醚处理后,SB203580减少磷酸化的p38 MAPK。SB203580也可以抑制茴香霉素(anisomycin)预处理诱导的神经保护[6]。
参考文献:
[1]. Miroslav Baranclk, Vierka Bohacova, Janka Kvackajova, et al. SB203580, a specific inhibitor of p38-MAPK pathway, is a new reversal agent of P-glycoprotein-mediated multidrug resistance. European Journal of Pharmaceutical Sciences, 2001, 14: 29-36.
[2]. Shuqiu Zheng and Zhiyi Zuo. Isoflurane Preconditioning Induces Neuroprotection against Ischemia via Activation of P38 Mitogen-Activated Protein Kinases. Molecular Pharmacology, 2004, 65:1172-1180.
[3]. Peter R. Young, Megan M. McLaughlin, Sanjay Kumar, et al. Pyridinyl Imidazole Inhibitors of p38 Mitogen-activated Protein Kinase Bind in the ATP Site. The Journal of Biological Chemistry, 1997, 272(18): 12116-12121.
[4]. Clare A Hall-Jackson, Michel Goedert, Philip Hedge, et al. E?ect of SB 203580 on the activity of c-Raf in vitro and in vivo. Oncogene, 1999, 18: 2047-2054.
[5]. Ana Cuadrado and Angel R. Nebreda. Mechanisms and functions of p38 MAPK signalling. Biochem. J., 2010, 429: 403-417.
[6]. Shuqiu Zheng and Zhiyi Zuo. Isoflurane Preconditioning Induces Neuroprotection against Ischemia via Activation of P38 Mitogen-Activated Protein Kinases. Mol Pharmacol, 2004, 65: 1172-1180.
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Storage | Desiccate at 4°C |
M.Wt | 377.44 |
Cas No. | 152121-47-6 |
Formula | C21H16FN3OS |
Solubility | insoluble in H2O; ≥18.872 mg/mL in DMSO; ≥3.28 mg/mL in EtOH with ultrasonic |
Chemical Name | 4-[4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-1H-imidazol-5-yl]pyridine |
SDF | Download SDF |
Canonical SMILES | CS(=O)C1=CC=C(C=C1)C2=NC(=C(N2)C3=CC=NC=C3)C4=CC=C(C=C4)F |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 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。溶液形式一般不宜长期储存,请尽快用完。 |
细胞实验[1]: | |
细胞系 |
Sf9细胞 |
溶解方法 |
在DMSO中的溶解度>10 mM。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。 |
反应条件 |
IC50:2 μM |
应用 |
在Sf9细胞中,编码v-Ras和Lck的DNA共转染可激活人c-Raf,其活性可直接用细胞裂解物测定或免疫沉淀之后测定。在Sf9细胞提取物中,SB 203580抑制c-Raf,IC50值为2 μM,比对SAPK2a/p38α的IC50值高40倍,但仅比SAPK2b/p38β2的IC50值高4倍。然而,在Sf9细胞、EGF刺激的小鼠Swiss 3T3细胞或EGF刺激的293细胞中,c-Raf免疫沉淀实验测得的IC50值要高10倍。 |
动物实验[2]: | |
动物模型 |
雌性Brown Norway大鼠 |
剂量 |
10-100 mg/kg;口服给药 |
应用 |
与对照组相比,SB 203580(10-100 mg/kg)口服给药对气道嗜酸粒细胞增多、BAL中性粒细胞增多和肺组织中嗜中性粒细胞基数均没有显著影响。BAL单核细胞/巨噬细胞的基数也不受SB 203580的影响(未挑战,对照组:443.8±36.2;挑战,对照组:414.1±29.7;挑战,SB 203580 100 mg/kg:381.5±41.8×103细胞/ml)。然而,SB 203580剂量相关地增加肺组织单核细胞/巨噬细胞的数量。 |
注意事项 |
请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。 |
References: [1] Hall-Jackson C A, Goedert M, Hedge P, et al. Effect of SB 203580 on the activity of c-Raf in vitro and in vivo. Oncogene, 1999, 18(12): 2047-2054. [2] Escott K J, Belvisi M G, Birrell M A, et al. Effect of the p38 kinase inhibitor, SB 203580, on allergic airway inflammation in the rat. British journal of pharmacology, 2000, 131(2): 173-176. |
描述 | SB203580是p38 MAPK的抑制剂,IC50范围介于0.3-0.5 μM之间,对SAPK3(106T)和SAPK4(106T)选择性低10倍,且阻断PKB磷酸化,IC50值为3-5 μM。 | |||||
靶点 | p38 MAPK | PKB | ||||
IC50 | 0.3–0.5 μM | 3–5 μM |
质量控制和MSDS
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